^8B 



Bli 1111 






1111 



""■■••'•' 

Bgjfir 






HI 



■Ml 



■Ab^s i 



Hi HSU -.; ; : 



S : s § ■ ' E 1 : gggl '. ; g - i § §£ ■ 




aiSKsseliwH 



?, s*»< 



m 



■■bEBbH 












* 




Class 

Book__ __ 
Copyright N? 



Gs 



COPYRIGHT DEPOSIT 



A TEXT BOOK 



ON 



URIC ACID 



AND ITS CONGENERS 



WITH SPECIAL REFERENCE TO ITS PHYSICAL AND CHEMICAL 
PROPERTIES, ITS METABOLISM 



AND 



ACCUMULATION IN THE ORGANISM 



TOGETHER WITH 

THE DISEASE PROCESSES ARISING THEREFROM AND THEIR 
.ETIOLOGICAL THERAPY 



FOR MEDICAL STUDENTS AND PRACTITIONERS 



BY 

GEORGE ABNER GILBERT, M. D. 

Member of Local, County and State Medical Societies of Connecticut; Physician to the Danbury 
Hospital, etc.; Once Fellow of the New York Academy of Medicine. 



FIRST EDITION 



1907 

THE DANBURY MEDICAL PRINTING COMPANY 
DANBURY, CONNECTICUT, U. S. A. 






LIBRARY Of CONGRFSSl 
Two Cooles Received i 



OCT 24 I90f 

. Copyright Ertrv 

CLASS' 4 XKc, No, 
COPY B. 



Entered according to Act of Congress, in the year 1907, by 

The Danbury Medical Printing Co., 

in the Office of the Librarian of Congress. All rights reserved. 



PREFACE. 

This volume is offered as a means of enabling 
physicians and students to better acquaint themselves 
with the fundamental principles of uric acid and its 
accumulation in the organism: a subject which every 
doctor is supposed to be somewhat familiar with, 
though one which is barely touched upon in any of 
our standard text-books. The need of such a work 
at the present time is almost imperative, not only on 
account of the vital bearing of the subject upon the 
ills of human kind, but in order that applicants for 
license to practice medicine may possess some medium 
for acquiring the specific information so often 
demanded of them. For instance, atone of the exami- 
nations, held not long ago by the New York State 
Medical Examining Board, among other interesting 
questions propounded in the Physiology paper occurred 
the following: " How is uric acid 'developed in the human 
system? What class of foods increases the development 
of uric acid?" A few years ago, physiologists would 
have been obliged to give quite different answers to 
these two questions than are given to-day. Yet the 
physician is supposed so keep himself fully abreast of 
the times and explain such mooted points satisfactorily. 
To do so, however, he must, perforce, seek assistance 
from various rare sources outside his library. He 
must have access to scores of foreign and domestic 
scientific medical journals, which have been issued 
from time to time during the past four or five years. 
Scattered throughout their numerous pages, he may, 



iv PREFACE. 

if sufficiently patient and persevering, find some highly 
instructive papers on the subject, written by profes- 
sional chemists and other experts. But he must be 
able to sift the "wheat" from the "chaff" — the "truth" 
from the "poetry." Many of the older chemical 
theories have been exploded; therefore, it is only by 
extensive and painstaking research through this form 
of literature that a proper understanding of the present 
status of the uric acid question can be formed. 

It is partly to fill thismanifest want that the present 
work has been published. In it have been brought 
together from all available sources the results of the 
experimental work of competent Swedish, French, 
German, Russian, English and American investiga- 
tors, the deductions from whose findings are presented 
as far as may be in a simple straightforward manner 
and from the most practical viewpoint. 

Few vital questions before the medical profes- 
sion to-day possess greater interest than does this of 
uric acid; and it has therefore been the aim here to 
furnish needed information along such lines as will 
enable the physician or student to better comprehend 
the subject and apply his added knowledge to some 
practical use. G. A. G. 

179 Main St., Danbury, Conn. 



TABLE OF CONTENTS. 



CHAPTER I. 
Its Place in Nature. page 

As a Nitrogenous Excrement 7 

As a Plant Food 8 

Anabolism vs. Catabolism 8 

Location in Vegetable Food 9 

Location in Flesh Foods 10 

Its Cumulative Action 10 

Its Power for Good or Evil 11 

CHAPTER II. 
Historical Review. 

Discovery of Uric Acid (1776) 13 

Early Chemical Findings (1 793-1848) 13 

The Early Medical Theory (1 797-1870) 14 

Garrod's Discovery (1848-1854) 16 

Garrod's Theory 17 

Early Xanthin Findings (1851-1889) 17 

Early Theory Exploded (1868-1893) 18 

Recent Findings (1 895-1905) 20 

CHAPTER III. 
Physical Characteristics. 

Isolation of Uric Acid 21 

Its Appearance 21 

Reaction 21 

Solubility 2 r 

Crystallization and Precipitation 23 

Attraction 25 

Ionic Dissociation 26 

CHAPTER IV. 
Chemical Properties. 

Composition of Uric Acid 27 

Its Acid Behavior 27 

Its Purin Structure 28 

Nuclein Cleavage 29 

Uric Acid Decomposition 31 

Synthetic Formation 33 

CHAPTER V. 
Physiological Processes. 

Endogenous Origin 37 

Exogenous Origin 38 

Catabolism 38 

Decomposition 39 

Catalysis 4° 

Circulation 41 

Excretion 43 

Egestion vs. Ingestion 44 

Purin Bases in Faeces 45 

Importance of the Subject 4° 

The Four Oxidases ., 47 



2 TABLE OF CONTENTS. 

CHAPTER VI. 
Purin Metabolism. page 

Definition 48 

Unbound Purins — Exogenous 48 

Bound Purins — Exogenous 49 

Fate of all Food Purins 50 

Pharmacologic Action 51 

Comparative Metabolism 53 

CHAPTER VII. 
Evolutionary Development. 

The "Special Creation" Theory 57 

The "Spencerian" Theory 58 

Transitional Stage 59 

The Decimal Decrease 62 

An Intermediate Product 64 

Muscle Metabolism 66 

Vis Inertice 67 

CHAPTER VIII. 
Accumulation in the Organism. 

Purin Removal 68 

Normal Finding of Uric Acid 68 

Its Presence a Menace 69 

Toxicity of the Purins 69 

Why Not Urea? 70 

Uric Acid Excess 70 

Purin Foods 72 

Tables of Exogenous Purins 73 

Meats 73, 74 

Vegetables , 74 

Beverages 74 

Miscellaneous 75 

White vs. Dark Meats 75 

CHAPTER IX. 
Accumulation in the Organism {Continued). 

Blood Alkalescence 77 

Urinary Acidity "... 78 

Weakened Reaction of Blood 79 

Deposition of Urates 80 

Effect of Alcohol 82 

CHAPTER X. 
Disease Processes. 

Purin Excess 84 

Its Three Stages 84 

(1) Uricacidremic Stage. 

Names 85 

Increased Viscosity 86 

Capillary Obstruction 86 

Localization of Symptoms 87 

Faulty Metabolism 87 

(2) Rheumatic Stage. 

Names 88 

Transition Period 88 

Localization of Symptoms 89 



TABLE OF CONTENTS. 3 

(3) Gouty Stage. page 

Definition 90 

Formative Period ^ 90 

Localization of Deposits 91 

CHAPTER XL 
(ij Uricacid/emic Manifestations. 

Pain 95 

Headache 96 

"Next Morning" Headache 97 

Fits of Blues 98 

Insomnia 99 

Headache Powders 100 

The Neuroses 102 

Periodicity of Symptoms 102 

CHAPTER XII. 
(2) Rheumatic Manifestations. 

The Beginning 104 

Muscular Stiffness 104 

Uric Acid Explosion 106 

Sites of the Deposits 108 

Leg Cramps no 

CHAPTER XIII. 

(3) Gouty Manifestations. 

Characteristics 113 

Genito-Urinary Concretions 113 

Concretions in Toe-Joint 115 

Other Tissues 116 

Objective Signs 116 

Experimental Production of Gout 117 

Intestinal Lithiasis 119 

Frequency of Gout 120 

CHAPTER XIV. 

Sequel.e and Complications. 

Constipation 122 

Hepatic Insufficiency 125 

Acid Dyspepsia 126 

Renal Inadequacy 127 

Urea Retention 129 

CHAPTER XV. 
Urinary Analysis. 

Ocular Inspection 131 

Alkaline Urine 133 

Retention of Solids 134 

Irritability of Neck of Bladder 135 

Hepatic Torpor 137 

CHAPTER XVI. 

Uric Acid Tests. 

Murexid Test 139 

Approximate Test 140 

Heat and Acetic Acid Test 140 

Heintz' Test 141 

Harley's Test 142 

Schiff's Test 142 

Dimrock and Branson's Method 142 



4 TABLE OF CONTENTS. 

PAGE 

Microscopic Examination 143 

The Complicated Tests 144 

The Uricometer 144 

Hall's Purinometer 145 

A Simple Test 145 

CHAPTER XVII. 

Bright's Disease. 

Definition 146 

Congestion 146 

True Bright's 146 

Renal Dialyzer 147 

Specialization 14S 

Localization 148 

Etiology 149 

Experiments upon Rabbits 151 

Deductions 152 

The Three Stages 154 

An Early Sign 155 

CHAPTER XVIII. 
Infants and Children. 

Uric Acid Infarcts 156 

Symptoms 157 

A Clinical Picture 158 

Uricacidaemic Signs 159 

Cyclic Vomiting 162 

Hematuria 162 

Lithiasis 162 

Albuminuria 163 

Asthma 164 

Rheumatic Signs 164 

Chorea 165 

Diagnosis 166 

CHAPTER XIX. 
Menstruation, Gestation and Menopause. 

Normal Menstruation 167 

Clinical Deductions 168 

Therapeutic Conclusions 1 69 

General Toxaemia 1 70 

Toxaemia of Pregnancy 171 

Morning Sickness 172 

Puerperal Eclampsia 1 74 

Prophylaxis 176 

The Menopause 177 

CHAPTER XX. 
Eye, Nose and Throat. 

Trend of Opinion 1 79 

Ocular Phenomena 1 79 

Iritis and Coroiditis 180 

Temporary Visual Irregularities 181 

Astigmatism 182 

Nasal Affections. . . 183 

Hay Fever 183 

Lithaemic Sore Throat 186 

Therapy 1 8fc 



TABLE OF CONTENTS. 5 

CHAPTER XXI. 
Traumatisms and Surgical Notes. page 

Joint Injuries 188 

The Interpretation , 190 

Other Traumatisms 191 

Sluggish Ulcers 192 

A Surgical Hint 192 

A Determining Factor 193 

CHAPTER XXII. 
Some Usually Unrecognized Uric Acid Conditions. 

Spine and Lower Extremities 197 

Symptoms 197 

Therapeusis 199 

Precaution 199 

Growing Pains 199 

Etiology 201 

Raynaud's Disease 202 

Local Signs 203 

The Uric Acid Theory 203 

Conclusions 205 

CHAPTER XXIII. 

Dental Conditions. 

The Teeth 207 

External Influences 207 

Protection 208 

Decay 209 

Uricacidoemia 21 r 

Toothache 212 

Later Stages 214 

CHAPTER XXIV. 
Haig's Work. 

His Three Books 217 

Their Popularity 217 

His Theory 218 

Concerning Drug Action 219 

Adverse Criticism 220 

His Mistake 221 

A Singular Contradiction 222 

Value to the Clinical Worker 224 

CHAPTER XXV. 
The Food Question. 

Effect of Environment 226 

Vegetarianism 228 

Modern Conditions 229 

Purin Feeding 230 

The Remedy 232 

CHAPTER XXVI. 
Dietetics. 

General Rules 234 

Uricacidaemic Patients 235 

Rheumatic Patients 237 

Chronic Cases 238 

Gouty Stage „ 242 

Evils of No-Flesh Diet 243 



6 TABLE OF CONTENTS. 

CHAPTER XXVII. 
Etiological Therapy. page 

Definition 245 

Exciting Etiological Factor 245 

Predisposing Etiological Factors 247 

Incidental Etiological Factors 249 

Summary 250 

CHAPTER XXVIII. 
Current Therapeutic Methods. 

Nosological Basis 251 

A Source of Therapeutic Error 252 

Symptom Therapy 253 

Its Limitations 256 

CHAPTER XXIX. 
Effect of Remedies in Common Use. 

A Frequent Indication 258 

Prevailing Custom 258 

Temporary Effects 259 

111 Effects 260 

Action of Drugs Used in Rheumatic Stage 262 

Effect of Salicylates 263 

Concerning the Alkalies 264 

CHAPTER XXX. 
Concerning Gout Therapy. 

Status of the Question 266 

Prevailing Type of Medication 268 

Use of Alkalies 270 

Effect on Genito-Urinary Concretions 272 

Laxative Effects 272 

CHAPTER XXXI. 
The Alkaline Eliminant. 

Definition 274 

Its Clinical Purpose 274 

The Objective Effect 270 

Its Solvent Effects 278 

Methods of Administration 280 

CHAPTER XXXII. 
Lithium. 

Solvent Properties 283 

Combined with a Laxative 284 

Sodio-Lithium 285 

Its Chemical Action 286 

CHAPTER XXXIII. 

Final Word. 
Autotoxemia Due to a Non-toxic Factor, 289; The Uric Acid Diathesis, 
290; Extent of Investigation, 290; Uric Acid Destruction, 291; Experiments 
Extra Corpus, 291; Croftan on the Rationale of the Alkaline Treatment, 292; 
Minkowski and von Noorden on Treatment, 293; Prof. Mendel's Discovery, 
294; Classification into Three Stages, 294; Uric Acid an Intermediate Product, 
295; Urea the End Product of Purin Catabolism, 295. 



URIC ACID 

AND 

ITS CONGENERS. 



CHAPTER I 



ITS PLACE IN NATURE. 



As a Nitrogenous Excrement. — Nitrogenous metab- 
olism is recognized to be one of the most important of 
life's vital processes, of which, in the animal kingdom, 
uric acid is one of the two essential end products. Though 
man and many other vertebrate animals give off their 
urinary nitrogen principally in the form of urea (86 per 
cent.), birds, insects and reptiles excrete theirs almost 
entirely as uric acid. 

Why uric acid should be the end product of tissue 
metamorphosis in some animals, and not in others, has 
long remained a mystery to the physiologist. It would 
seem only rational, however, in the light of modern evo- 
lutionary science, to conclude that the excretions of animals 
must necessarily correspond with the individual structural 
environments of such excretions — i. e., their respective 
anatomical organs. The mammal, with its kidneys and 
accessory genital organs, has reached an anatomical 
evolutionary development which necessitates its nitrog- 
enous waste being presented in a more soluble form — i. e., 
urea. In other words, a morphological structure like the 



8 URIC ACID AND ITS CONGENERS. 

kidney, and a physiological excretion like urea, necessarily 
go hand in hand— evolve pari passu. 

The fowl and serpent, and other oviparous animals 
(those that spawn or lay eggs), have never been evolved 
to the stage requiring a special urinary apparatus, there- 
fore there is no necessity of their nitrogenous excreta 
being presented in the more highly oxidized form of urea; 
for, inasmuch as the ureters end in a common cloaca with 
the rectum, it may pass out with the feces in the less solu- 
ble form of uric acid. It has been noted, too, that the 
red blood corpuscles of all oviparous animals contain nuclei 
— not observed in the red globules of mammals. 

As a Plant Food. — The complementary and anti- 
thetical relationship existing between the metabolic pro- 
cesses of the animal and vegetable kingdoms is often very 
strikingly illustrated. The animal, for instance, exhales 
carbon dioxid, and inhales oxygen: the plant absorbs the 
former and gives off the latter. One furnishes what the 
other needs. 

In a similar manner the fruits of plants serve as a food 
for animals, while the excrement of animals serves as a food 
for plants. For years, guano has been used by the agri- 
culturist as a fertilizer. The guano of commerce is obtained 
from the islands off the coast of Peru, to which large 
flocks of sea-birds resort. It is chiefly composed of their 
excrement in a decomposed state and consists principally 
of uric acid in the form of ammonium urate. 

Anabolism vs. Catabolism. — The nitrogen, or 
ammonium content (NH 4 ), of uric acid (probably nitrate 
of ammonium), is utilized bv the plant as a food-essential 
which either is combined with, or is instrumental in the 
combining of other elements, to form and elaborate tissue 



ITS PLACE IN NATURE. 9 

structure. It is a singular fact that plants have the power 
of building up or forming from the simple inorganic ele- 
ments in Nature, the complex organic structures of which 
they are composed and which serve as food for animals. In 
short, their metabolic process is chiefly a synthetic process. 

Animals do not possess this power. On the contrary, 
they take the complex substances already built up by 
plants, which, in becoming a part of the animal organism 
(i. e., digested, absorbed and assimilated), are decomposed 
into their original elementary parts. The metabolic pro- 
cess in animals is chiefly an analytical process. 

The plant, as may be seen, utilizes uricacid as a food 
constituent; while the animal excretes it as useless waste. 
In this way, this substance has become an important factor 
in the cycle of life: in the anabolism of vegetable tissue and 
the catabolism of animal tissue. 

Location in Vegetable Food. — Uric acid does not, 
of course, occur, as such, in plants. It is synthesized to an 
allied form of purin or xanthin. It is located where we 
would naturally expect: in the vitalizing or fecundating 
organs of the plant, i. e., in the germinating seeds, ovules 
and leaves — as in coffee and tea, peas and beans. In short, 
it is found in the parts analogous to the secreting organs of 
animals — the vegetative or reproductive parts: where it 
appears, in one, an active source of metabolism, and in the 
other as a passive result. 

The uric acid or ammonia derivative, in plants, exists 
as an "alkaloid"; as theobromin (from cacao beans 
and seeds of theobroma cacao); caffein or theophyllin 
(from seeds of the coffee tree or from tea leaves) ; morphin ; 
codein; narcotin; quinin; strychnin; veratrin; atropin; 
etc. In animals, the analogous bases from which uric 



10 URIC ACID AND ITS CONGENERS. 

acid is metabolized, are guanin, xanthin, hypoxanthin, 
adenin, etc. 

Location in Flesh Foods. — By "flesh food," we 
mean the flesh or meat of dead animals. The blood and 
tissue-juices of these dead animals contain the waste debris 
salts (uric acid, xanthins, etc.), which the animal was about 
to excrete, and would have excreted as useless had it not 
been killed. This waste, therefore, cannot be considered 
as a food proper, since it has already been cast off from the 
disintegrating or dying cells of the animal. 

Again, the nuclein of the cellular tissues of the animal 
(composing muscle-fibers and glands) must also be decom- 
posed after ingestion, into its cleavage products, the xan- 
thins, thus serving as another food-source for uric acid. 
In one case, the xanthins already exist as free bases in the 
tissue-juices of the dead animal; in the other, they are 
organically combined with the nucleinic acid of the 
nuclein, but are, of course, set free during the analytic 
process of digestion. Like the alkaloids of the plant 
(which are often taken in the form of drugs), these flesh 
xanthins or purins can only serve to stimulate or irritate 
temporarily, by causing extra effort on the part of the meta- 
bolic organs to oxidize them (into uric acid or urea) and 
effect their removal from the system. 

Its Cumulative Action. — From what has been said, 
it will be seen that uric acid is obtained from the foods of 
the vegetable kingdom, as an alkaloid, xanthin, purin, or 
extractive of plants; and from foods of the animal king- 
dom, as an alkaloid, xanthin, purin, or extractive of meat. 
When introduced into the system, by ingestion of flesh food 
or of vegetable food of the character described, it acts much 
like any other alkaloid, in the form of a drug: not as a food 



ITS PLACE IN NATURE. 11 

proper. Like morphin and certain other alkaloids, it has 
a cumulative action, so that the person who has been 
accustomed to eating flesh, drinking coffee, etc., may be- 
come suddenly and unexpectedly poisoned from an "ex- 
plosion" of its effects, and he will also, probably, become 
an habitue — that is, his sympathetic nervous system will 
crave its accustomed irritant or stimulant. It is, therefore, 
a difficult matter, or perhaps impossible, for the meat eater 
to turn at once into a vegetarian. It is like giving up the 
"drink" habit or "drug" habit. 

Its Power for Good or Evil. — Of course, the 
human organism is obliged to rid itself of the uric acid 
resulting from the breaking down of its own bodily cells, 
as well as of that of the cleavage products derived from the 
nuclein of flesh ingested as food; so that the metabolic 
and excretory organs are made sufficiently active in per- 
forming their essential duty, without introducing gratui- 
tously more work of a similar character by means of free 
xanthins, ready formed, which can serve no useful purpose 
as. food. We are prone to ingest substances into the 
organism, in this way, which are quite unnecessary and 
superflous, thus causing extra eliminative effort to get rid 
of them — as in the case of alcohol, drugs, tobacco, etc. 

The power of uric acid for good or evil probably 
resides chiefly in its nitrogen or ammonia content, which 
will be beneficial to the plant and injurious to the animal. 
An analogous power is inherent in carbon dioxid, which 
the animal exhales as poisonous and the plant absorbs as a 
nutrient. 

It will be seen, then, that, though uric acid has an 
important place in Nature, this place is not as a food for 
man. On the contrary, like carbon dioxid, and like am- 



12 URIC ACID AND ITS CONGENERS. 

monia in other combinations than that of the ureids proper, 
it is excreted from the animal body as useless waste, which 
becomes harmful if retained. In fact, it may be decom- 
posed into carbon dioxid, ammonia and glycocoll. Its true 
office, then, is to serve as an excrement for animals and a 
fertilizer for the reproduction and growth of plants. It is a 
nitrogenous ash, thrown off by the analytical processes 
(catabolic) of animal life, to be taken up and utilized by the 
synthetic processes (anabolic) of vegetable life. 

In conclusion, it may be stated that the excreta of 
plants are altogether of gases, so that waste substances 
resulting from the cell life of the plant must remain in its 
tissues. Such products are always removed to parts in 
which they cannot interfere with the vital activities of the 
plant; so that such "extractives" are found in the bark of 
plants, skins of seeds, etc. 



CHAPTER II. 

HISTORICAL REVIEW. 

Discovery of Uric Acid (1776).— Though the his- 
tory of uric acid, during its 130 years' ups and downs* 
contains (until very recently) but few American names of 
note, the year that marks its beginning has a distinct 
American sound. 

In 1776, two years after his discovery of oxygen, Karl 
Wilhelm Scheele discovered uric acid in a concrement; 
and, in the same year, Prof. T. Olof Bergman found the 
substance in a cystitic calculus. Both were well-known 
Swedish chemists, whose names have become famous for 
their important discoveries in chemical science. The 
collected works of the latter were published in 1779-84; 
those of the former, in 1793. 

Early Chemical Findings, (1 793-1848). — For a 
number of years after this discovery of uric acid, chemical 
experts were interested in its study, and it was soon found 
to be a normal constituent of human urine. 

In the same year that Scheele published his volumi- 
nous work, (1793), Comte de Fourcroy, a well-known 
French chemist, found urea to be one of the decompo- 
sition products of uric acid; and, four years later (1797), 
William Hyde Wollaston, the celebrated English chemist 
and physicist (who afterward discovered the ultraviolet 
rays of light), found uric acid in the form of its insoluble 
salts in the concretions of gout. 

The next two names to be connected with these earlier 
uric acid studies are familiarly known to physicians and 
students in every part of the civilized world; viz., Prof. 



14 URIC ACID AND ITS CONGENERS. 

Friedrich Wohler and Baron Justus von Liebig, the two 
illustrious German chemists, who associated themselves 
together for scientific research in the early part of the 19th 
century. Wohler, who is generally recognized as the 
"Father of Organic Chemistry," demonstrated, in 1828, 
the possibility of forming a product of the living organism 
(i. e., urea) from inorganic material (ammonium cyanate). 
Liebig was professor of chemistry at Giessen, where he 
established his laboratory for researches in organic chemis- 
try, and afterwards published his famous "Dictionary of 
Chemistry." In 1838, these two scientists, by their com- 
bined investigations, were enabled to point out conclu- 
sively the singularly close relationship borne by uric acid 
toward urea, allantoin and alloxan. 

Ten years later (1848), it was shown by Wohler and 
Frerichs that when uric acid was introduced as such into 
the organism, some of it was transformed into urea, on 
excretion. 

The Early Medical Theory (1 797-1 870). — The 
knowledge gained concerning uric acid and its intimate 
relationship to urea, soon set medical men to speculating 
on the probable similarity of origin of the two substances 
and their probably analogous mode of formation in the 
body. As urea was known to be the end product of albu- 
min metabolism, as well as an oxidation product of uric 
acid, it was reasonable to suppose that the latter was also 
derived from albumin and represented an intermediate 
stage in the process. For many years it was believed by 
medical men, and was so taught by physiologists (and even 
many physicians today have not learned to the contrary) 
that normally all albumin passes through a uric acid stage 
in being oxidized into urea. 



HISTORICAL REVIEW. 15 

From this, it was only a step further to believe that 
any increase of uric acid must result from faulty albumin 
metabolism, the process being interrupted at the uric acid 
stage owing to insufficient oxygenation. Anything which 
interfered with the normal oxidizing processes of the body, 
such as disturbances of the circulation or of respiration, 
was considered responsible for the increase of uric acid. 

This theory obtained so firm a foothold that experi- 
mental investigators were, as a rule, prone to make the 
mistake of looking only for such clinical evidence as seemed 
to be confirmatory. In other words, facts were made to 
harmonize with the theory, rather than vice versa. 

In support of this suboxidation theory, Virchow, in 
1847, directed notice to the abnormal amount of uric acid 
in leukaemia. Six years later, Lehmann's popular i Text- 
book of Physiological Chemistry" appeared, in which it 
was taught that uric acid is a half-way stage in the oxi- 
dation of albumin into urea. In Vol. I, of the German 
Archives of Clinical Medicine, published in 1866, Bartels 
advanced his famous hypothesis of the "relative" insuffi- 
ciency of oxygen as in pneumonia and certain fevers to 
account for the increase of uric acid, known to be present 
in these conditions. 

About this time, numerous feeding experiments by 
different investigators corroborated Wohler's finding that 
uric acid, when fed to dogs and man, is given off in the 
urine largely as urea. This experimental finding was con- 
sidered convincing proof of the correctness of the albumin- 
metabolism theory. The fact did not seem to be appre- 
ciated then, as it is now, that though the experiment proved 
that uric acid may be burned into urea, this does not neces- 
sarily mean that all uric acid is thus burned, or that all 



16 URIC ACID AND ITS CONGENERS. 

urea is thus derived. As a matter of fact, it is known that 
only a small proportion of urea represents burned up uric 
acid, and only a certain proportion of uric acid is burned 
into urea. 

Garrod's Discovery (1848-1854). — The uric acid 
finding, to which we have now come, is one which has 
profoundly influenced all subsequent studies and investi- 
gations of the subject. Though, as already mentioned, 
Wollaston had discovered uric acid salts in the concretions 
of gout, fifty years previously, the connection between uric 
acid and gout was not worked out. To Sir Arthur Garrod, 
the palm must be awarded for showing the relationship 
between the two. 

In 1848, in a paper on "The Blood and Urine in Gout, 
Rheumatism, and Bright's Disease," read before the 
Medico-Chirurgical Society of London, Garrod demon- 
strated that the blood of gouty patients contains urate 
salts in excess. In determining the presence of an excess of 
uric acid in the blood, he introduced his famous "thread 
test"; to wit: — A little blood is collected in a watch crystal 
and some dilute acetic acid added; in this mixture a linen 
thread is immersed and the whole set aside to stand for 
twenty-four hours, evaporation being prevented. At the 
end of this time, if there is an excess, crystals of uric acid 
are thrown out, adhere to the thread, and can be easily 
recognized under the microscope. 

By the application of this test, it was shown by Garrod 
that the blood of gouty patients contains uric acid in an 
abnormally large amount. His findings were subsequently 
confirmed by several well-known investigators (Ranke, 
Charcot, Bence-Jones, Salomon, and others) and more 
recently by Klemperer and Strauss, who used the more 



HISTORICAL REVIEW. 17 

accurate Ludwig-Salkowski method, for determining uric 
acid in the blood by gravimetric analysis. 

Garrod's Theory. — Though the knowledge of the 
mode of formation of uric acid in the body was still incom- 
plete and faulty at the time of Garrod's discovery, yet the 
theory he formed concerning the aetiology and pathology of 
gout is accepted by many authorities even today. He con- 
sidered that the gouty nodes and tophi are derived pri- 
marily from an excess of uric acid in the blood, and that the 
tissue lesions in the affected parts are caused by the 
deposition of urates. He held that, in gout, there is 
deficient elimination on the part of the kidneys, the alka- 
linity of the blood plasma is lessened, and consequently the 
blood is no longer able to hold the uric acid combination 
in solution. The latter, in the form of the biurates, is 
suddenly deposited in and about the joints, where an in- 
flammatory action of the contiguous soft tissues is effected. 

Early Xanthin Findings (1851-1889). — As early 
as 1 85 1, Scherer published his findings of hypoxanthin in 
the .spleen and in the blood of leukaemic subjects; and, 
during the next four or five years, experts began to recog- 
nize the chemical resemblance between uric acid and the 
xanthins. In 1858, Ranke suggested that inasmuch as 
uric acid and hypoxanthin were both present in splenic 
juice and were increased in amount in leukaemia, the two 
substances possibly had a similar origin, hypoxanthin 
being an earlier stage than uric acid in the metabolic pro- 
cess. In 1 87 1, the expert, Salkowski, put forth strong argu- 
ments against the albumin-metabolism theory and offered 
in its stead the hypothesis that uric acid is derived from 
xanthin bases and the spleen; but the time was not yet ripe 
for the acceptance of this new doctrine. 



18 URIC ACID AND ITS CONGENERS. 

Pure chemists now began those remarkable experi- 
ments with nucleins and their cleavage products. In 1874, 
Miescher isolated nucleinic acid from the sperm of salmon 
and showed that xanthin bases resulted as decomposition 
products. Again, in 1879, Kossel obtained xanthin, hypo- 
xanthin, adenin and guanin from nuclein; showing, more- 
over, that they are not present in nuclein as free bases, but 
organically combined with the nucleinic acid. Two years 
later he suggested that these bases were probably fore- 
stages of uric acid; and, the following year, he offered as 
an argument that the muscles of birds and reptiles (whose 
chief metabolic end product is known to be uric acid) are 
much richer in hypoxanthin than are the muscles of mam- 
mals. 

It will be seen that these studies were gradually lead- 
ing up to the discovery of the fact that uric acid is derived 
from the nucleins and xanthin bases, as demonstrated by 
Horbaczewski in 1889, when he performed his classic 
experiment of squeezing spleen pulp, mixing with it 
defibrinated blood, passing air through it and finding large 
amounts of uric acid formed. He believed that he was 
warranted in declaring that uric acid was an oxidation 
product of nuclein (only of leucocytes, he thought) through 
its xanthin cleavage products. This was an important 
finding, inasmuch as it led to the discovery of the true 
origin and mode of formation of uric acid in the body. 

Early Theory Exploded (1 868-1 893). — Little at- 
tention was at first paid to those experimental findings 
which threatened in any way to disprove the theory that 
albumin, in being metabolized in the body, passes through 
a uric acid stage, and that the latter is increased whenever 
there is deficient oxidation. Increase of uric acid excretion 



HISTORICAL REVIEW. 19 

following the ingestion of meat, pointed to a nitrogenous 
origin; and, until certain chemical discoveries were made, 
that origin was naturally thought to be albumin. 

As early as 1868, Senator cast some doubt on the sub- 
oxidation theory, by showing that permanently constricting 
the thorax of animals, thus limiting their oxygen intake, 
did not increase the uric acid excretion. In short, inter- 
ference with respiration did not necessarily mean uric acid 
increase, though it did mean deficient oxygenation. Again, 
it was shown by other investigators that anaemia, produced 
experimentally, did not cause increased uric acid excretion; 
and, furthermore, that there was no evidence of the oxi- 
dizing processes being diminished in leukaemia. 

It was also shown by Minkowski and others that the 
feeding of pure albumin foods had no direct relation to- 
ward uric acid increase. The death-knell to the albumin 
theory was not sounded, however, until Kossel (1893) 
demonstrated that meat increased uric acid excretion 
owing to the abundance of free xanthins it contained. In 
other words, it finally became understood that uric acid 
was not derived from the albumin of meat, but, as shown 
by Kossel, Burian and Schur, and others, from the nuclein 
and free xanthin bases, especially of glandular meats 
(sweetbread, liver, etc.). 

Horbaczewski had been the first to point out, by his 
feeding experiments, that nuclein produced an increase of 
uric acid excretion within two hours after its ingestion. 
Professional chemists now abandoned the albumin theory 
— they recognized the fact that uric acid metabolism and 
albumin metabolism were carried out along two entirely 
different lines; but it took medical men some time to learn 
that the old established theory had been exploded. 



20 URIC ACID AND ITS CONGENERS. 

Recent Findings (1895-1905). — During the last 
decade many important discoveries have been made con- 
cerning the origin, destruction, and mode of formation of 
uric acid in the body, under normal conditions. It has also 
been shown how the metabolism of uric acid becomes 
changed under certain pathological conditions and thus 
gives rise to disease. These various findings, relating to 
the precipitation of urates out of solution, their faulty ex- 
cretion, retention and accumulation in the organism, will 
be considered in detail under their proper headings in the 
body of this work. 



CHAPTER III. 



PHYSICAL CHARACTERISTICS. 



Isolation of Uric Acid. — The most convenient way 
of isolating uric acid in its purity, is to submit the excre- 
ment of snakes to a simple chemical process, the details of 
which may be found described in any text-book of phy- 
siological chemistry. It can also be separated from human 
urine by the employment of a somewhat more complicated 
though similar analytic method — i. e., by concentration 
and addition of hydrochloric acid. 

It was first prepared synthetically by Horbaczewski, 
in 1882, by treating a mixture of glycocoll and urea at a 
high temperature. It has also been obtained synthetically 
by heating a mixture of urea and trichlorlactic acid. 

Its Appearance. — Pure uric acid is tasteless and 
inodorous. It is a glistening, snow-white, crystalline 
powder, which, under the microscope, appears to consist of 
minute (though regular) transparent, colorless crystals, 
in the form of rhombic plates, with rounded angles, and 
often united in pretty rosettes. They may be whetstone, 
dumb-bell, paddle, and spiculated shaped, and of a reddish 
or yellow-brown color, due to the accompanying pigment 
(usually purpurine). They may be seen by the naked eye 
in the urine, as "sand," " gravel, " "brick-dust," and "red 
pepper grains." 

Reaction. — Uric acid slightly reddens blue litmus, 
as it is a tasteless, weak acid. 

Solubility. — Uric acid itself is less soluble than 
most of its salts. It is practically insoluble in dilute acids, 



22 URIC ACID AND ITS CONGENERS. 

alcohol, ether water, or strong solutions of alkaline car- 
bonates. It dissolves in i : 40,000 parts, cold water, and 
in 1 : 1,800 parts, boiling water. 

It is soluble in weak alkaline solutions: therefore, 
alkaline urine and blood hold uric acid in solution. 

In a solution containing both uric acid and the soda 
phosphates (as in the urine and blood), the uric acid is 
precipitated by the acid phosphates, and held in solution 
by the basic or neutral phosphates. 

Uric acid does not occur, as such, in the normal urine, 
but rather in the form of its more soluble salts or urates — 
principally with the alkali metals, sodium and potassium. 
Being a dibasic acid, it is capable of forming two series of 
these salts — neutral urates and acid urates, the former 
being more soluble than the latter. The urates, therefore, 
that we see precipitated from urine, passed in normal 
quantity, are the acid urates. 

Uric acid may be precipitated in the form of its 
characteristic crystals, owing to its liberation from union 
with sodium or potassium, during the period of the so- 
called "acid fermentation," when the urine reaches its. 
greatest acidity (i. e., a few hours after voidance). The 
neutral urates may also, at the same time, be converted 
into acid urates and thus precipitated. Even in fresh 
urine, if the urates are excessive in amount, or if the urine 
be too acid or too small in quantity to hold the urates in 
solution, the latter will be deposited in the form of sedi- 
ment. Under the same conditions, they may be precipi- 
tated in the bladder before voidance, thus being passed as. 
gravel. 

Heat dissolves the urates; cold precipitates them. 
Thus being more soluble in warm than in cold solutions, 



PHYSICAL CHARACTERISTICS. 23 

the urine may be clear on voiding, but deposit quite a 
sediment on cooling. This precipitate will be dissolved by 
heating the urine, which will serve to differentiate it from 
other precipitates. 

The urinary urates are usually spoken of as the 
" amorphous," or " acid," or " mixed " urates. They rarely 
appear in crystalline form, though small needles are some- 
times found. As one author says: "The usual form is a 
rather dense, sandy deposit, cream-colored, yellow, pink or 
rose-colored, or even brown, depending on the color of the 
urine. Under the microscope, small sandy particles are 
seen, usually yellowish or brownish, with now and then a 
crystal of uric acid. A drop of caustic soda or potash added 
to the sediment on the slide, will cause it to dissolve 
immediately. On the other hand, a drop of hydrochloric 
acid added to the sediment will in two or three minutes 
produce very small colorless crystals of uric acid." 

Crystallization and Precipitation. — One of the 
most significant of the physical characteristics of uric acid 
is «its strong tendency, when in solution or suspension, to 
crystallize out on contact with any solid substance, as may 
be noted on the bottom and sides of the vessel containing 
it. This characteristic has been observed often enough, 
so far as trie urine is concerned; but it is so common a 
phenomenon that its significance has been generally over- 
looked or disregarded. 

Garrod discovered this same tendency on the part of 
uric acid, when in solution or suspension in the blood, to 
crystallize out and become attached to a solid substance 
introduced — as witness his "thread test." The precipi- 
tation of the crystalline urates in the joints of the toe, where 
the circulation is sluggish, is probably due in some measure 



24 URIC ACID AND ITS CONGENERS. 

to this same factor. The same principle holds good, too, 
as applied to other solid tissue-structures, where the urates 
show a predilection to become deposited. 

In gouty concretions, the uric acid crystals have been 
formed from the insoluble acid urate or biurate of soda — 
more correctly called "mononatrium (or monosodic) 
urate." Laboratory experiments have demonstrated the 
fact, that, if a solution of sodium hydrate (NaOH) be 
added to a liquid holding uric acid in solution or sus- 
pension, the mononatrium urate (acid urate or biurate of 
soda) will be thrown down as a precipitate; and that, after 
all the uric acid in the liquid has been thus united with the 
soda, the mononatrium urate is itself transformed, by the 
further action of NaOH, into the dinatrium urate (neutral 
urate of soda), and as this is soluble, it is at once dissolved. 
Now, from this solution of neutral urate, if acid of any kind 
be added, the uric acid will fall out as a precipitate — as it 
does in the gouty joint, where the tissue-juices are subject 
to sudden variations in their alkalinity. 

It has been shown in these studies, that the monona- 
trium urate precipitate (biurate), first thrown down as 
above described, occurs in the form of transparent amor- 
phous spheres, which, on standing, are gradually trans- 
formed into needle-shaped crystals — this being simply an 
alteration in physical form and not a change in chemical 
composition. "These amorphous spheres," as one author 
states, "yield with water certain opalescent (or even clear) 
false solutions — the so-called colloidal solutions; such 
colloidal solutions may contain an enormous quantity of 
urates, far more than can be dissolved in the same quantity 
of water to make a genuine solution. On standing, the 
colloidal solutions gradually give rise to saturated genuine 



PHYSICAL CHARACTERISTICS. 25 

solutions, and the excess of urates present then falls out in 
the form of the crystalline salt." — (Jour. A. M. A., Mar. 
II, 1905.) 

The significance of these findings as applied to uratic 
deposits in certain pathologic conditions, can hardly be 
overestimated. It is probable that the colloidal urates in 
the blood pass through a similar process, prior to their 
precipitation in crystalline form; for it is observed that 
they are thrown out in those localities where the capillary 
circulation is most sluggish or where stasis exists, and 
where the blood and its contents are brought into direct 
contact with the surrounding solid tissue-structures. 

Attraction. — Another so-called peculiarity, ob- 
served in studying the physical chemistry of uric acid, is 
the tendency of its crystals to attract other urate crystals. 
So far as we know, Haig was the first to direct attention to 
this phenomenon and give it practical application, al- 
though we presume that the crystals of most other salts act 
in a similar manner toward their sister crystals. 

."By throwing a little powdered uric acid on a filter,' ' 
says Haig, "and pouring a urine (acid in reaction) twice 
quickly through it, it is possible to abstract almost every 
particle of uric acid from that urine — which remains in 
combination with the solid uric acid on the filter." On the 
other hand, if sufficient alkali be added to the urine to 
make its reaction alkaline, before pouring it on, instead of 
giving up its uric acid, it absorbs to itself all the solid uric 
acid that was on the filter. 

The importance of this finding or discovery may be 
utilized in practical therapeutics. For instance, the uratic 
deposits or concretions in the tissues may be likened to the 
filter, with its powdered uric acid, in the experiment; 



26 URIC ACID AND ITS CONGENERS. 

while the blood is substituted for the urine. If, now, we 
can succeed in increasing the alkalinity of the blood suffi- 
ciently, which bathes the parts containing the deposits, it 
may be possible to absorb some of the solid uric acid from 
this so-called filter. 

Ionic Dissociation. — A further possibility of, at least, 
partially absorbing these solid precipitates has recently 
been suggested to us by the exhaustive studies of Paul 
and His, Jr., into the physical chemistry of uric acid. 
They have shown that when an aqueous solution of uric 
acid is being formed, the two available hydrogen atoms of 
the molecule of uric acid are dissociated in some such anal- 
ogous manner as when its salts with the alkali metals are 
formed. Either one or two hydrogen ions are formed 
(especially the former), as well as the resulting univalent 
or bivalent molecular anions. The more dilute the solution, 
the greater the degree of this dissociation. 

It was found that the number of undissociated mole- 
cules in the solution is proportional to the number of free 
hydrogen ions; and, as the former are very insoluble, they 
are thrown down as a precipitate. The number of hydro- 
gen ions are, of course, increased by the addition of an 
acid, (as HCl), which means also a greater number of un- 
dissociated molecules and their consequent precipitation. 
To aid the solubility of uric acid, therefore, our aim is not 
only to increase the alkalinity of the solution, but to de- 
crease the number of hydrogen ions: and this may be 
accomplished by means of the introduction into the 
solution (the blood) of such hydroxyl radicles (OH) as will 
take up the former to make H 2 0, thus resulting in the 
formation and excretion of water, with diuresis, and its 
accompanying molecules of uric acid in solution. 



CHAPTER IV. 



CHEMICAL PROPERTIES. 



Composition of Uric Acid. — Uric (or lithic) acid is 
composed of the four chief elements in nature — carbon, 
hydrogen, nitrogen and oxygen — whose atoms are com- 
bined in the following ratio to form the molecule, C 5 H 4 
N 4 3 . Uric acid is, therefore, composed of 31.8 per cent, 
nitrogen, by weight. 

Its Acid Behavior. — It has been found to be one of 
the chief chemical characteristics of this substance to act 
as an organic acid base — i. e., being capable of readily 
combining with the alkali monometals to form salts. In 
short, it is a dibasic acid with the formula H 2 (C 5 H 2 N 4 
3 ). It will be seen that it has two H atoms, which may 
be exchanged for two monometal elements. These two 
available hydrogen atoms of pure uric acid are usually 
replaced by one or the other of the alkali metals, sodium or 
potassium, or it may be by ammonium. With lithium, its 
most soluble salt (dilithium urate) is formed. 

The two H atoms may be saturated with two atoms of 
sodium, forming dinatrium urate (neutral urate of soda), 
Na 2 (C 5 H 2 N 4 3 ). Or, the monometal may displace but 
one atom of the H, forming mononatrium urate (biurate 
of soda), NaH (C 5 H 2 N 4 0,)y 

In his famous lectures ori the chemistry of uric acid, 
published at London, in 1892, Sir W. Roberts makes the 
claim that a monometal may take but one of the four dis- 
placeable H atoms, in two molecules of uric acid, forming 
heminatrium urate (what he calls "quadriurate" of soda) 



28 URIC ACID AND ITS CONGENERS. 

NaH(C 5 H 2 N 4 3 ),H 2 (C 5 H 2 N 4 3 ). He is of the opin- 
ion that it is in this form of the "quadriurate" (which 
is very soluble) that uric acid circulates in the blood. But, 
according to the more recent findings of two competent 
chemical experts, TuniclifFe and Rosenheim, (Cf. Lancet, 
LXXVIII, 1900, p. 1708) this is only a hypothetical salt 
and probably has no actual existence. They suggest that 
Roberts may have been dealing with variable mixtures of 
uric acid and mononatrium urate. 

Its Purin Structure. — Structurally, uric acid may 
be regarded as a purin derivative. The word "purin" is 
applied to various nitrogenous substances, which are 
derived from animal and vegetable cells, and which contain 
the hypothetical chemical molecule, C 5 H 4 N 4 , a sub- 
stance discovered by Emil Fischer, who made it synthet- 
ically and called it "purin" (purum uricum), since by the 
replacement of its various hydrogen atoms by the radicles, 
hydroxyl (OH), or amino (NH 2 ), or alkyl (CH 3 ), etc., a 
large number of important derivatives are obtained, such 
as the various nuclein (alloxuric, xanthin or . purin) 
"bases," uric acid, caffein, theobromin, theophyllin, etc. 

All of these purin bodies contain the group, C 5 N 4 , 
the so-called "purin nucleus." The atoms in this group 
are arranged thus: 

N 1 C 6 

I I 
C 2 C 5 N 7 X (purin nucleus) 



N 3 C 4 N 9 , 



C 8 



It will be seen from the rational formula (given below) 
of uric acid, that it consists of the purin nucleus, with one 



CHEMICAL PROPERTIES. 29 

hydrogen to each nitrogen atom (forming "purin"), and 
three oxygen atoms attached to three of the carbons, one 
to the second atom, one to the sixth atom and one to the 
eighth atom, thus suggesting the chemical name, "2, 6, 
8-trioxypurin," with the formula: 

HN CO 

I I 

CO C NH\ (Uric Acid) 

I II CO 

HN C NH/ 

Hypoxanthin (C 5 H 4 N 4 0), xanthin (C 5 H 4 N 4 2 ), and 
uric acid (C 5 H 4 N 4 3 ), are known respectively as mono-, di- 
and tri-oxypurin; while adenin andguaninare called amino- 
and amino oxy-purin;andcaffein and theobromin known as 
trimethyl- and dimethyl xanthin. It will be observed that 
uric acid is a purin derivative, oxidized a step furtherthan 
xanthin or hypoxanthin, containing one more oxygen atom 
than the former and two more than the latter. This fact is 
further shown by the laboratory experiments of Kossel and 
Salomon, who have demonstrated that uric acid is produced 
when the nuclein of* yeast or of leucocytes is heated in the 
presence of air; but, if the air is excluded, the xanthin 
bodies are produced instead. Furthermore, it is known to 
physio-chemists, that venous blood generally contains a 
small proportion of xanthins, while arterial blood contains 
uric acid and scarcely[any xanthins. 

Nuclein Cleavage. — These various xanthin bases, 
or extractives, may exist either as "free" substances in 
partial solution (as in meat juice or gravy), or may be 
"bound" together with the other constituents of the 
nuclei of cell protoplasm (as in the nucleins or nucleo- 



30 URIC ACID AND ITS CONGENERS. 

proteids of glandular tissue), from which they may be 
readily obtained as cleavage products. 

The nucleins (or nucleo-proteids) contain albumin 
and nucleinic acid, the latter of which, on hydrolysis, is 
oxidized into xanthin bases and thyminic acid (the latter 
yielding phosphoric acid and a carbohydrate complex). 
For example, on digestion with pepsin-hydrochloric acid, 
the nucleo-proteids yield protein (albumin) and an in- 
soluble residue of true nucleins, which, on further cleavage 
with dilute mineral acids, yield proteins (albumins) and 
nucleinic acids, which may undergo further splitting into 
xanthin (or alloxuric) bases and thyminic acid. These 
relations are shown in the following schema: 

Nucleo-proteid 

/\ 

Albumin Nuclein 

/\ 

Albumin Nucleinic Acid 

/ \ 

Xanthin Thyminic 
bases acid 

The common xanthin or purin derivatives of nucleinic 
acids are xanthin, hypoxanthin, guanin, and adenin. From 
these, in turn, may be derived heteroxanthin, paraxanthin, 
theophyllin, theobromin, caffein, epiguanin, and carnin. 
But three of the latter (heteroxanthin, paraxanthin and epi- 
guanin) have thus far been found in the urine. Caffein, 
theobromin, and theophyllin, occur only in the vegetable 
world. The remaining members of the group are common 
constituents of both animal and vegetable cells. Collec- 



CHEMICAL PROPERTIES. 31 

tively they are termed "purin," "xanthin," or'^alloxuric' 
bases. They are all closely related to each other and to 
uric acid — which is a further oxidized nitrogenous end 
product; for, of the total purin nitrogen (0.265 grammes) 
normally excreted in the urine, by far the greater portion 
(o.22lTgrammes) is in the form of uric acid, the remainder 
being xanthin base nitrogen. 

Uric Acid Decomposition. — Thus far, it has been 
shown that the purin nitrogen, excreted in the urine as uric 
acid, is oxidized either directly from the free xanthin bases, 
or indirectly from the nucleins or nucleo-proteids. But 
not all of the uric acid thus derived and formed in the bodv 
becomes excreted in the urine : some of it undergoes further 
decomposition before excretion, and appears in the urine 
in the form of urea principally, and to a slight extent in the 
form of one or more of the urea derivatives. 

In short, so far, we have considered that portion of 
uric acid, derived as a decomposition product from the 
purins, which is eliminated from the body as uric acid 
without further change: now, we will consider it as a 
decomposition product of the purins, just as before, but 
devote our attention to that considerable portion (50 per 
cent.) which undergoes further change, and is excreted 
from the bodv in the form of urea, or one of its derivatives. 
In the former sense, uric acid is considered simply a 
" purin" body; in the latter it is not only a purin, but a 
"ureid," and is so classed. 

The ureids are nitrogenous, crystallizable bodies, 
which, on hydrolytic decomposition alone, or on simul- 
taneous oxidation, yield urea. Hence they are derivatives of 
urea. Their chemical resemblance to the xanthins is 
shown, when uric acid is treated with an oxidizing agent in 



32 URIC ACID AND ITS CONGENERS. 

the presence of water, when it gives rise to the same pro- 
ducts as do the xanthins; to wit: 

(i) C 5 H 4 N 4 3 +0+H 2 0=C 4 H 2 N 2 4 +CH 4 N 2 
uric acid alloxan urea 

(2) C 1 H 2 N 2 4 +2H 2 0=C 3 H 2 3 +CH 4 N 2 
alloxan mesoxalic urea 

acid 

The relationship of uric acid and other ureids to the 
xanthins is further shown by decomposing both with 
hydrochloric acid or hydriodic acid under high pressure. 
The same products are obtained in each instance, viz: 
ammonia, carbon dioxid and glycocoll. 

On decomposition, the ureids yield either urea and a 
non-nitrogenous acid (containing three carbon atoms) 
directly, or they give rise to urea and a less complex ureid, 
which is then further decomposed as in the first instance. 
They are all related to each other and, as we have seen, to 
the nucleinic or xanthin bases from which they are in part 
derived. The mono-ureids (i) are alloxan, dialuric acid, 
hydantoin, parabanic acid, oxaluric acid, etc. The di- 
ureids (2) are uric acid, purpurate of ammonia (murexid), 
allantoin, hydurilic acid, etc. The former generally con- 
tain two nitrogen atoms in the molecule; the latter, four. 

With hydrochloric acid, under special conditions, uric 
acid yields glycocoll, carbon dioxid and ammonia. With 
nitric acid, it yields first alloxan, and later parabanic acid 
and carbon dioxid; the parabanic acid then goes on to 
oxaluric acid and later still to oxalic acid and urea. 

With permanganate of potash, uric acid in neutral 
solution at moderate temperature, is split to allantoin and 



CHEMICAL PROPERTIES. 33 

carbon dioxid; and the allantoin, on oxidation, yields urea 
and oxalic acid; to wit: 

(i) C 5 H 4 N 4 3 +H 2 0+0=C 4 H 6 N 4 3 +C0 2 

uric acid allantoin 

(2) C 4 H 6 N 4 3 +2H 2 0+0=C 2 H 2 4 +2 CH 4 N 2 

allantoin oxalic acid urea 

The presence in the animal body of urea, glycocoll, 
oxalic acid, and allantoin, has often been demonstrated. 
^Synthetic Formation. — The preparation of uric 
acid in vitro, through the union of two of its decomposition 
products, glycocoll and urea, has often been accomplished 
in the laboratory during the last five or six years; and, as a 
consequence, it has been suggested by chemists that this, 
or some similar synthetic process, may take place inside 
the animal body. As an outcome of his experiments to 
determine the method of formation of uric acid in the liver 
of birds, Wiener has come to the conclusion that a small 
proportion of the uric acid, normally produced in the 
human organism, is formed synthetically in the liver by the 
union of tartronic acid (C 3 H 4 5 ) with two urea radicles 
and the intermediate formation of dialuric acid (as in the 
laboratory experiment) — the tartronic acid itself being 
derived from lactic acid by oxidation. E. Schmoll has 
advanced a similar theory. 

While the postulating of such a synthetic reduction 
process to account for the hypothetical formation of uric 
acid by synthesis in the body, may prove satisfactory to the 
chemical expert; yet, to us, it seems contrary to Nature's 
plan that a catabolic waste product should be built up in 
this way, before excretion, out of its own decomposition 



U URIC ACID AND ITS CONGENERS. 

products, or, in fact, out of any other oxidation products. 
Then, again, we can see no necessity for erecting such an 
fhypothesis, since all of the uric acid normally excreted as 
a result of cellular metabolism can be accounted for in the 
msual manner, — by oxidation of the purins. 

The catabolic products, which represent disintegra- 
tion and death of tissue cells in the animal kingdom (i. e., 
•change from living to non-living matter), are the result of a 
tearing down process, not a " building up " process. There- 
fore, if we are to consider uric acid in the light of a nitrog- 
enous waste product, as the ash of "burned up" material 
iresulting from oxidation, it is evident that it will be ex- 
creted from the body as such, or as still further oxidized 
into urea or its derivatives. It seems strange that Nature 
should reverse the usual order of things, and take the un- 
necessary pains of forming a waste substance out of its own 
decomposition products. Furthermore, the liver (where 
this synthetic formation is said to take place) is known to 
furnish an oxidase which decomposes uric acid into urea — 
exactly vice versa. 

Some physio-chemists, it is true, accept Wiener's 
suggestion of a uric acid formation in the liver by syn- 
thesis; but they cannot consistently consider the uric acid 
thus formed to have been produced normally as a catabolic 
waste tissue product. It seems a bit singular that physiol- 
ogists should accuse the liver of decomposing uric acid into 
urea and its derivatives, and, at the same time, of recom- 
posing urea and its derivatives into uric acid — i. e., as part 
and parcel of a like metabolic process. In the higher 
■orders of the animal kingdom it is not the plan of nature to 
'"build" her cast-off tissue material, — such excrement is 
Heft for the plant to synthesize. 



CHEMICAL PROPERTIES. 35 

While, therefore, we cannot believe that that con- 
siderable portion of uric acid which results from cellular 
decomposition and expenditure of energy in the body, and 
is excreted in that sense as a nitrogenous waste product of 
tissue catabolism, is ever formed synthetically in the liver; 
yet, it is possible, of course, that some may be thus formed 
directly out of certain chemical derivatives introduced into 
the stomach, — though the purins, and uric acid itself, when 
thus introduced, are usually chiefly oxidized by the liver 
into urea. We know, however, that the liver actually does 
perform both oxidations and syntheses; but the latter 
process is usually done to keep toxic substances from enter- 
ing the general circulation and reaching the body tissues — 
substances which have been brought to the liver by the 
portal vein from the stomach and upper intestine. 

In his experiments with hens and mammals, Wiener 
fed them urea derivatives and a dibasic non-nitrogenous 
acid (containing three carbon atoms), and observed an 
increase of uric acid excretion, (especially in the case of the 
hens), thus concluding that uric acid, in this case, was 
formed synthetically out of its decomposition products. 
This may be true; but the uric acid thus formed is not 
representative of nitrogenous catabolism, nor of any other 
ordinary normal catabolic process. On the contrary, it 
represents the crowning act of a special digestive process 
which the liver is sometimes called upon to perform in its ca- 
pacity as a sentinel, to prevent toxic substances from en- 
tering the general circulation — i.e., substances which have 
inadvertently, or for experimental purposes, been intro- 
duced into the stomach. Should these same decomposi- 
tion products be thrown from the tissues into the circula- 
tion, owing to some unknown pathogenic condition, they 



36 URIC ACID AND ITS CONGENERS. 

would probably be carried to the liver and synthesized in 
this same way; but this, of course is not physiological — 
it is pathological. 



CHAPTER V. 

PHYSIOLOGICAL PROCESSES. 

Endogenous Origin. — From the convincing feeding 
experiments of Mares, in 1892, and from those of Burian 
and Schur, Hall and others, more recently, it has been 
shown that a considerable proportion (probably one-half), 
of the purin nitrogen excreted in the urine as uric acid and 
xanthins, is normally produced in the organism from 
muscle metabolism and the catabolic destruction of the 
nuclear cellular tissues throughout the body. Owing to 
Horbaczewski's teachings, it was first thought that only 
the nucleins of the leucocytes were thus catabolized; but it 
is now known that the purin bodies are derived from the 
broken down nuclei of all body cells. 

It has been demonstrated by O. Lowi that, in mam- 
mals, the nuclear uric acid, under physiological conditions, 
is derived principally from the cells of those organs or 
tissues which undergo most active chemical changes — as 
the secretory organs. The blood of children contains a 
greater number of leucocytes than that of adults, con- 
sequently more uric acid is formed and excreted by 
children proportionate to their body weight. 

That the nuclein of cells is not the only source of 
endogenous uric acid, will at once be seen when remember- 
ing that the six or eight grains of the latter contained in the 
twenty-four hours' urine (and an equal amount destroyed 
in the body) would necessitate the destruction of fully six 
ounces of nuclein — an enormous daily cell destruction. 
Burian has recently shown that a great portion of the 



38 URIC ACID AND ITS CONGENERS. 

endogenous uric acid excreted in the urine arises from the 
oxidation of hypoxanthin, which is a constant product of 
muscle metabolism. 

Exogenous Origin. — The uric acid derived from the 
nucleins and xanthins ingested with food, drink and drugs,, 
is considered to be of exogenous origin. Like that which 
results from disintegration and death of the cells within the 
body, the uric acid derived from foods is obtained in great- 
est amount from the nucleins of glandular organs — as 
sweetbread, liver, etc., and from the so-called "extractives" 
or juices of meat, which contain "free" xanthin bases in 
considerable amount. More is derived from thymus and 
liver than from brains and kidneys. 

Of the 0.06 per cent, of the purin bodies present in 
meat, no less than 0.045 P er cent - is in a free state — mostly 
hypoxanthin. It was found by Minkowski that fifty per 
cent, of the hypoxanthin contained in muscle, liver and 
spleen, and twenty-five per cent, of that in thymus, (and a 
smaller per cent, of the adenin) when fed to man, was 
excreted as uric acid. Many of the vegetable alkaloids are 
chemically allied xanthins, which likewise serve as a 
source of uric acid. For instance, when coffee is ingested, 
one-third of its caffein (trimethylxanthin) is excreted as a 
purin body. 

Catabolism. — Physiologists are now generally of the 
opinion that uric acid is evolved not only in the liver, but in 
the various other organs and nuclear tissues of the body, as 
in muscles, kidneys, spleen and blood. Spitzer, Kowalew- 
ski, and others, have pointed out that the xanthins are 
found in these several localities, and that uric acid is doubt- 
less formed there. But this only means that cell destruc- 
tion goes on everywhere, and that the xanthin cleavage pro- 



PHYSIOLOGICAL PROCESSES. 39 

ducts resulting from such destruction are oxidized still 
further into uric acid before removal from the immediate 
neighborhood of the cell destroyed. In short, it simply 
means a continuation of the disintegrating process — a 
further change from living to non-living matter. 

Not all of this purin waste, however, is metabolized in 
this way into uric acid before removal into the general 
venous circulation; for, it is known that venous blood con- 
tains xanthins, whereas arterial blood contains little or 
none. It would seem, then, that at least some of the cata- 
bolic xanthins are not transformed into uric acid at the 
place of cell death, (owing, says Burian, to "poverty of 
oxygen"), but enter the circulation to become metabolized 
elsewhere into uric acid. This doubtless takes place chiefly 
in the liver; for we know that the xanthins ingested into 
the stomach are carried by the portal vein to the liver and 
there changed into uric acid or urea. It has been proven 
that the liver not only metabolizes into uric acid the xan- 
thins derived from the breaking down of its own cells, but 
also, the xanthins brought to it from other sources. It is 
doubtful if the other organs and tissues possess this extra- 
metabolic function. 

Decomposition. — Reasoning by analogy and judging 
from the experiments of Ascoli, Croftan, and one or two 
others, to determine this point, it is thought that that 
portion (40 to 60 per cent.) of uric acid which is known to 
be decomposed in the body and excreted in the urine in the 
form of urea or its derivatives, is destroyed in the same 
organs and tissues where it has already been metabolized 
from the xanthins. But if this be true, it can be true only 
of endogenous uric acid; since that which is derived from 
the food and then destroyed, is destroyed in the liver, being 



40 URIC ACID AND ITS CONGENERS. 

brought to the latter by the portal vein from the stomach 
and small intestine. 

This latter assumption would seem to be true when it 
is considered that most of the uric acid, ingested as such 
into the stomach, is excreted in a very short time as urea. 
It is further corroborated by the careful and exhaustive 
investigations carried on conjointly by Soetbeer and 
Ibrahim, who have demonstrated by their experiments 
(Cf. Hoppe-Seyler's Zeitschnft fur physiol. Chemie, March 
20, 1902), that, when uric acid is injected subcutaneously, 
much of it is eliminated as uric acid. This indicates that 
the general tissues do not oxidize exogenous uric acid into 
urea — a power possessed chiefly by the liver. 

In short, transformation of exogenous xanthins into 
uric acid, and of exogenous uric acid into urea, is doubt- 
less a digestive process, not a catabolic process; therefore, 
such process takes place in the principal digestive organ, 
the liver, — perhaps to some extent also in the spleen- 

Catalysis. — It has been shown that various tissue 
extracts, particularly those of the liver and spleen, con- 
tain an oxidase capable of bringing about the conversion 
of xanthin and hypoxanthin into uric acid. R. Burian 
has studied also the action of the hypoxanthin-oxidase 
of muscles, in changing the products of their metabolic 
activity, and broken down tissue cells into uric acid. He 
has found that the conversion takes place, not in the 
muscles themselves, but just as the hypoxanthin is passing 
from the muscle-fibre into the surrounding lymph. 

The production of hypoxanthin is increased when the 
muscle is at work; therefore, the hypoxanthin and uric 
acid, leaving the muscle, are likewise increased in amount. 
That some of the hypoxanthin leaves the muscle in this 



PHYSIOLOGICAL PROCESSES. 41 

way, without being changed into uric acid, is probably 
due, as Burian says, to the fact that the hypoxanthin- 
oxidase cannot act efficiently on account of lack of oxygen. 
Doubtless the same thing occurs in other organs and 
tissues; though sufficient oxygen will soon be furnished 
the blood, in its passage through the lungs, to enable the 
oxidation process (into uric acid or urea) to be completed 
before final excretion. 

It is now generally claimed by physio-chemists, and on 
good grounds, that the oxidase of the liver is capable of 
transforming uric acid into urea or allantoin, or both. It 
should be remembered, therefore, that not all of the urea 
present in the urine represents albumin-metabolism, but 
that some of it is the result of purin-metabolism. Of 
course, it will be understood that urea is a product of 
nitrogenous metabolism in both instances. 

Circulation. — Professional opinions are many and 
divergent concerning the physical and chemical form in 
which uric acid circulates through the body. All agree, 
however, that uric acid does not occur, as such, in the 
blood, but in combination with something else, as in the 
form of a salt. 

It is contended by Schmoll and a few other observers, 
that, normally, the majority of it is combined with thy- 
minic acid, or in loose union with some organic atom 
complex, and, therefore, that it is unrecognizable in that 
form by any of our present qualitative tests: only when 
separated from this combination, as in certain diseased 
conditions (gout, etc.), can it be detected, in which form it 
may be precipitated out of solution. 

Others accept Roberts' teaching, that under normal 
conditions uric acid occurs in the blood as a "quadri- 



42 URIC ACID AND ITS CONGENERS. 

urate," — the heminatrium urate, which is readily soluble. 
Still others think that it is held in the blood in imperfect 
solution or suspension with the sodium salt, in the form 
of mononatrium urate, having combined with the sodium 
of the carbonates or phosphates present in the blood. 

We believe that Haig has reached an adumbration of 
the truth, when he describes uric acid in solution in the 
normal phosphates of the blood stream, in which there 
are also probably present some alkaline salts of soda or 
potash; and that, under certain conditions, this uric acid 
combination circulates in the form of a colloid or gelat- 
inous material. This latter idea was suggested to him 
by watching, day after day, the extremely slow and tedious 
filtration of the gelatinous urate of silver through the 
asbestos fibre-filter as used in Haycraft's process for the 
estimation of uric acid. It occurred to him that the capil- 
laries of the body might be said to resemble the interstices 
of the filter and that uric acid might be present in the 
blood in some similar gelatinous form, which would ex- 
plain a number of clinical phenomena not otherwise 
accounted for. 

As stated in a previous chapter, when treating of the 
subject of "Crystallization and Precipitation," we know 
from laboratory experiments, that a liquid holding uric 
acid, when added to a solution of sodium, (as the blood), 
gives rise to the formation of amorphous spheres of mon- 
onatrium urate, which yield with water a so-called "col- 
loidal" solution, in which a greater quantity of uric acid 
may be held than in a saturated genuine solution. It is 
not improbable, therefore, that when the uric acid is 
metabolized and brought in direct contact with the al- 
kaline carbonates of the lymph and blood plasma, a com- 



PHYSIOLOGICAL PROCESSES. 43 

bination with the sodium takes place in some such manner 
as above described, thus resulting in its circulation in the 
body, (through the capillaries, at least, where the journey 
is first begun and the current is most sluggish), in this 
peculiar colloid form. 

Excretion. — Normal urine (excretion in the 24 hours) 
contains from 0.2 to 0.8 grammes of uric acid, and one- 
tenth as much of the xanthins. That a much greater 
quantity of uric acid would appear in the urine if it were 
not changed into urea by the liver, is shown by the fact 
that a greatly increased elimination of it occurs (nine times 
as much, according to Hahn and Nencki) when the blood 
of the portal vein is prevented from flowing through the 
liver by establishing a so-called Eck fistula between this 
and the inferior vena cava, and when the hepatic artery 
is at the same time ligated. 

"In this manner, the blood of the spleen and the 
extensive lymph districts of the intestinal tract," says 
Simon, "is carried directly into the general circulation 
and- the combined xanthin bases and uric acid find their 
way into the urine without being subjected to the action 
of the oxidases of the liver. We may hence conclude, " 
says he, "that the appearance of these bodies in the urine 
is under normal conditions owing to the fact that not all 
of the blood of the body reaches the liver before being 
carried to the kidneys." The latter organs simply act 
as a physiological filter or dialyzer through which pass the 
urates which are brought thence for final excretion. 

The urates are always held in solution in fresh, nor- 
mal urine, but, upon cooling, or after standing a few 
hours, they may be deposited owing to a reaction between 
the mononatrium urates and mononatrium phosphate of 



44 URIC ACID AND ITS CONGENERS. 

the urine, resulting in the formation of dinatrium phos- 
phate and free uric acid. 

The solubility of uric acid and urates in the urine is 
dependent on their relations to the neutral or dinatrium 
phosphates present. The latter possess the power of pre- 
venting the decomposition of urates into free uric acid, 
while the tendency of mononatrium phosphate is to cause 
their decomposition. It is ineffective, however, as long as a 
sufficient amount of the dinatrium phosphate is present 
along with it. 

Egestion vs. Ingestion. — It has been shown by 
the elaborate feeding experiments of I. Walker Hall, of 
England, that the addition of foods (containing known 
quantities of purin bodies) to a purin-free diet, results in 
an increased egestion of urinary purin, but that the latter 
is not equal to the quantity ingested. A considerable 
proportion (40 to 60 per cent.) is not accounted for. To 
account for this balance, physiologists are now generally 
agreed that the ingested purin is first oxidized to trioxy- 
purin (uric acid), and that a portion of this is later de- 
composed by the liver and finally excreted as urea. L6wi> 
Neumeister, and other experimenters, have arrived at 
this same conclusion, demonstrating that the liver of car- 
nivorous animals and of man possesses the power of oxi- 
dizing exogenous uric acid — the former into allantoin, the 
latter into urea — by means of a ferment, or "oxidase." 

It is further assumed that not all of the purin of en- 
dogenous origin (i. e., from cellular catabolism) is ex- 
creted as such, but that a proportion is oxidized by the 
liver, in the manner above stated, into urea. Ascoli dis- 
covered the uric acid destroying power of the liver as 
follows: He mixed blood with uric acid or with lithium 



PHYSIOLOGICAL PROCESSES. 45 

urate and first determined that blood alone did not possess 
the power of destroying uric acid if kept at body tempera- 
ture for several days. He then passed a mixture of blood 
and uric acid through a fresh dog's liver that was kept 
at body temperature and discovered that a considerable 
loss of uric acid occurred. At the same time he discovered 
a great increase of a urea-like substance. 

In a series of carefully conducted experiments, E. W. 
Rockwood, (Cf. Amer. Jour, of Physiol., Sept. I, 1904) 
has shown that the endogenous output of uric acid is 
variable for different individuals, but constant in quantity 
for the same person — more constant, in fact, than the 
elimination of either nitrogen or phosphoric acid. 

Purin Bases in F^ces. — Though the amount is 
small and variable, it is, nevertheless, true (as shown by 
both Hall and Schittenhelm), that the normal feces of 
man always contains purin bodies. If the dry fecal resi- 
due is considerable, the amount of purin bodies is rela- 
tively high. Their presence is evidently due in part to 
desquamation of the epithelial cells of the intestinal walls. 
They are also derived from food rich in nuclein, such as 
thymus, which always increases the quantity of fecal 
purin. 

Though generally found in meconium, uric acid 
itself is seldom found to any great extent in the feces of 
extra-uterine life. (This is contradicted by Galdi, who 
shows by recent experiments that the feces of man normal- 
ly contains about 25 mg. uric acid excreted daily). The 
purin bases in the feces are chiefly present in the free 
state, though a small percentage is combined with nuclein. 

While the purin bases occur regularly in the pancre- 
atic secretion, they are rarely found in bile, unless the 



46 URIC ACID AND ITS CONGENERS. 

biliary passages are inflamed. Adenin and guanin are 
abundant in the walls of the intestines, together with 
smaller amounts of xanthin and hypoxanthin, and it is 
probably from this source that a considerable percentage 
of the purin bases in feces is derived. The balance doubt- 
less represents the unabsorbed purins contained in the 
nucleins of ingested food. 

It has been observed that, when exposed to the action 
of putrefactive organisms, adenin is transformed into 
hypoxanthin, and guanin into xanthin, so that these two 
are only found in decomposed material. 

Importance of the Subject. — As recently pointed 
out by Prof. R. H. Chittenden, of Yale, in an address 
delivered before the Massachusetts Medical Society, June 
13, 1905, (Cf. Boston Medical and Surgical Journal, Aug. 
17, 1905), we know more about the intermediary pro- 
cesses and products of purin metabolism in the animal 
economy, than of any other of the metabolic functions. 
Nucleoproteids are conspicuous in all cells of the body 
and in all tissues, — glands, muscles, etc. Their wide- 
spread distribution indicates their great physiological im- 
portance; and, in consequence, their metabolism must of 
necessity be a conspicuous feature in the changes taking 
place in all glandular organs. The importance of the 
study of uric acid formation and decomposition at once be- 
comes manifest. In other words, it is easy to see, as Chit- 
tenden says, " how perversion or inhibition of intermediary 
metabolism of uric acid may be engendered by causes 
which act primarily upon the cells where the enzymes (ox- 
idases) have their origin, or by influences which may bring 
about changes in the environment surrounding the intra- 
cellular ferment. " 



PHYSIOLOGICAL PROCESSES. 47 

The Four Oxidases. — In summing up, it is made 
quite clear how various intra-cellular enzymes, working 
one after the other, are able gradually to evolve uric acid 
from tissue nucleo-proteids; to wit: 

I. Under the influence of a nuclease, nucleic acid is 
split up with liberation of the free nuclein bases. 2. Then 
by the action of a deamidizing enzyme, guanase or ade- 
nase, guanin and adenin are transformed into xanthin and 
hypoxanthin, respectively. 3. Further, by the action of 
xanthin-oxidase (Burian), hypoxanthin is oxidized to 
xanthin, and the latter is converted into uric acid. 4. 
Finally, it is to be noted that there is another tissue oxi- 
dase, contained, so far as is known at present, in the liver, 
kidneys, muscle, and, perhaps, the marrow of bones 
(Schittenhelm), which has the power of oxidizing and 
thus destroying uric acid, i. e., decomposing it into urea 
or its derivatives. This is known as the uricolytic ferment 
(Mendel). 

"Here, then," says Chittenden, "we have four dis- 
tinct enzymes or intra-cellular ferments, more or less 
responsible agents for the production and presence of 
uric acid in the body." 



CHAPTER VI. 



PURIN METABOLISM. 



Definition. — The term "metabolism" has been 
applied to the assemblage of transformations which a 
constituent of the organism undergoes in its passage 
through the body. By the term "purin metabolism" we 
mean (i) the various chemical changes which purin-con- 
taining substances undergo within the body from the time 
of their ingestion as food or drink until their egestion from 
the body as waste; and (2) the physiological processes by 
which purin waste is derived from destructive metamor- 
phosis, or the "wear and tear" of the nuclear tissue ele- 
ments themselves. 

Unbound Purins — Exogenous. — By " unbound ' 
or "free" exogenous purins, is meant those oxypurins, 
aminopurins or methylxanthins (xanthin, hypoxanthin, 
guanin, adenin, caffein, theophyllin, etc.) which occur as 
such in food, drink or drugs, not combined with the other 
constituents (phosphoric acid, albumin, etc.) that go to 
make up the nuclein of the cell nucleus, or the proteid of 
the cell protoplasm. From the careful analyses made by 
many investigators, it has been shown that the purin- 
content of beef, veal, ham, chicken and other flesh meats, 
occurs chiefly (75 per cent.) in the unbound or uncombined 
form; and that, though an equal amount of free purins 
also occurs in glandular organs (liver, thymus, sweet- 
bread, etc.), yet the percentage is reversed, there being 
three times as much of the bound purins, instead of one- 
third as much. In vegetable foods the unbound purins 



PURIN METABOLISM. 49 

are rarely found. In certain drugs, however, such as 
caffein, the purins have been extracted from their proteid 
holding in a chemically pure form, and are, therefore, 
"free." 

Ordinarily, owing to the process of cooking, and 
action of heat, the unbound purins of meat are largely 
extracted in solution, in the form of gravy, soup, or in that 
of "beef extract," the remaining fibrous or muscular 
portion containing the bound purins. If the steak or 
"bake" be only medium done or rare, a considerable 
portion of the free purins still remain behind in the tissue- 
juices. 

It will be seen that the unbound purins of uncooked 
meat represent that catabolized or decomposed portion 
of the nucleo-proteids which the animal was about to ex- 
crete as useless waste from the system at the time it was 
butchered; and, therefore, are necessarily found in the 
blood and tissue-juices of the meat. Most of these free 
purins are the oxypurins (hypoxanthin and xanthin), 
though a small quantity of the amino-purins may be found 
in glandular tissue, — adenin in the pancreas, and guanin 
in the thymus gland of young veal. 

Bound Purins — Exogenous. — In the nuclear cellular 
tissue of glands, the "bound" purins of food substance 
occur in greatest abundance, the purin ring being bound to- 
gether with the nucleic acid to form the nuclein or nucleo- 
proteid. As will be readily understood, the bound purins, 
in this form, comprised part of the living proteid tissue of 
the muscles and glands of the animal at the moment of its 
death; they had not yet become catabolized into purin 
waste, or "free" purins. Immediately after death, how- 
ever, and before the tissues can be utilized as food, autoly- 



50 URIC ACID AND ITS CONGENERS. 

sis or auto-digestion takes place (especially in glandular 
tissue), and certain of the already partially catabolized 
nucleins undergo further decomposition into free purins. 
The "free" adenin and guanin present in the living gland, 
are almost entirely decomposed into hypo-xanthin and 
xanthin respectively, immediately after the animal's death. 
For this reason the amino-purins are usually found only 
bound together in the nuclein molecule of food substances. 
The methyl-xanthins (cafFein, theophyllin, etc.), are found 
chiefly in the vegetable world. 

Fate of All Food Purins. — It should be well under- 
stood at the outset that the purins ingested in food or 
beverage pass through the body in a few hours without 
having served any useful purpose. They are not assimi- 
lated into the tissues, are not utilized for the production of 
cell nuclein, exert no direct influence on either carbohy- 
drate or nitrogenous metabolism — "they indirectly in- 
voke an output of metabolic energy to insure their early 
removal from the body." (Hall). In short, they are 
simply further oxidized, decomposed and excreted. 

As the "free" purins (with the possible exception of 
guanin) are readily dissolved in the intestinal juices, they 
are absorbed unchanged (mostly as hypoxanthin and xan- 
thin) into the portal circulation and carried to the liver, 
where they are oxidized into uric acid (40 to 60 per cent.) 
and urea (40 to 60 per cent.), and thus conveyed through 
the general circulation to the kidneys and- excreted. A 
very small portion escapes this oxidation and is excreted 
in the urine as xanthin. 

The uric acid portion, above mentioned, is excreted 
within eight hours after ingestion of the purin, and the 
smaller xanthin portion within four hours. This would 



PURIN METABOLISM. 51 

seem to indicate that "free" purin metabolism, in the 
healthy organism, is by no means sluggish. It should 
be stated in this connection that a considerable portion of 
the ingested guanin (probably 50 per cent.) passes un- 
changed through the intestine and is excreted in the feces. 

When " bound" purins are ingested, a small percent- 
age is decomposed in the intestine into "free" purins, and 
appear partly as such in the feces and are partly absorbed; 
but the greater part of the nuclein is directly absorbed as 
such into the circulation and undergoes decomposition 
and final oxidation into uric acid and urea, in the same 
manner and proportion as already described: the only 
difference being that, in this case, the phosphoric acid and 
albumin radicals which are split off from the purin ring of 
the nuclein molecule, doubtless become utilized in the 
process of cell construction. 

In the case of the " bound" purins, the uric acid ap- 
pears in the urine within a day or two after ingestion of the 
food, depending on the activity of the circulatory and 
metabolic organs. According to the carefully conducted 
feeding experiments of Hall, the system excretes in urine, 
within forty-eight hours, one-half of the fish, fowl and beef 
purin in food. It was found, in some instances, that the 
purin of beans is excreted the same day as eaten. 

From the foregoing findings, it will be seen that the 
" bound" purins of food require a more prolonged meta- 
bolic effort than do the "free" purins, to insure their oxi- 
dation, decomposition and excretion from the body; thus 
being contra-indicated in all cases in which the digestion 
is weak and faulty, especially in children. 

Pharmacologic Action. — The fact that the purins 
pass through the body in so short a time, would seem to 



52 URIC ACID AND ITS CONGENERS. 

show that the danger arising from their ingestion may not 
be due so much to the direct irritation caused by their 
actual presence at this time, as to the fact that they may 
become only imperfectly excreted, — in short, that the 
principal danger is from their retention and accumulation. 
It should be understood, however, that adenin and guanin 
(owing to their amino radical )are directly irritating to the 
mucous lining of the gastro-intestinal tract, and may give 
rise to inflammation. Adenin is a violent poison, and, 
whenever retained in the glandular tissue, invariably 
gives rise to histological changes of grave importance. 
To a lesser degree, the same is true of the oxypurins, 
though a longer time is required to produce the results. 

Among the principal effects noted, when the chemi- 
cally pure xanthins are ingested, may be mentioned the 
following: i. The salivary secretions and gastric juice 
are increased in amount (more watery), though the fer- 
ments themselves are not correspondingly increased. 2. 
The methylxanthins, in large doses, tend to induce reflex 
irritability and muscular contraction or rigidity (due to 
the nitrogen group, same as in ammonia compounds), and 
slight diuresis. 3. The amino-purins are directly irritant. 
4. Uric acid, itself, in single large doses, daily, will, in 
three or four days, produce a condition simulating malaria. 

Kochmann has recently fed several dogs on ox-flesh 
alone for six to ten weeks. In all of them the liver showed 
cloudy swelling and fatty infiltration. Fatty degeneration 
and parenchymatous inflammation of the kidneys were 
also observed. His conclusions indicate that excessive 
flesh food may (like alcohol and lead) cause deficient liver 
metabolism, kidney degeneration, and the consequent 
alterations in the excretion of uric acid. 



PURIN METABOLISM. 53 

"At present," says Hall, (The Purin Bodies in Food 
Stuffs, page 78), "there is a tendency to disregard the 
action of the oxypurins upon the tissues but it must be 
remembered that when they are in excess they probably 
form unusual combinations and that such products may 
act as irritants. When Kochmann added carbohydrate 
food to the meat diet, his dogs presented fewer post-mor- 
tem pathological changes. Up to the present date, I have 
made a large number of personal experiments, and when I 
have taken large doses of purin bodies — such as 8 grains 
of hypoxanthin, 15 grains of guanin, 8 to 15 grains of uric 
acid, — apparently associated symptoms of general mal- 
aise and irritability have frequently appeared." 

Comparative Metabolism. — Experiments upon dif- 
ferent animals have given findings that would seem to 
indicate (if we have properly interpreted their meaning), 
that, as we rise in the mammalian scale, the metabolic 
activity of the intracellular ferments and glandular oxi- 
dases is correspondingly increased. This is shown to 
some extent in the action of the general tissues, but more 
particularly in that of the liver, — the chief metabolic organ 
or oxidizing depot. 

In cats and dogs, the liver has reached a certain stage 
of development in oxidizing or destroying uric acid, — an 
oxidizing stage in purin metabolism that is one round 
lower than that of which the human liver is capable. In- 
travenous injections of lithium urate in the cat leads to 
much excretion of allantoin, a ureid intermediate between 
uric acid and urea. Similar experiments upon dogs show 
that their liver is capable of oxidizing uric acid into allan- 
toin; while, under the same conditions, the human liver 
continues the oxidation a stage further, — to urea. 



54 URIC ACID AND ITS CONGENERS. 

If sulfonal be given to cats and dogs, at the time of 
the above mentioned experiments, thus interfering with the 
oxidizing power of the liver, the process stops short of the 
allantoin stage, and uric acid is excreted instead; while, 
in man, the process stops short of the urea stage, and evi- 
dences of allantoin appear in the urine. 

The presence of allantoin instead of urea, in the urine 
of cats and dogs under special conditions, indicates a lower 
stage of metabolic evolution than that reached by man. 
Reasoning from analogy, it would appear that the presence 
in the human urine of uric acid at all, is due to incomplete 
decomposition of the purin ring, and indicates that the 
time may come when the human liver, aided by the then 
more highly specialized tissues, will be enabled to change 
all nitrogenous substances (purin as well as albumin) into 
urea. Uric acid is certainly an intermediate product, 
formed during the oxidation of the purin radical, which 
has been split off from the nuclein molecule of cellular 
tissue, — the end product of which is urea. The more 
active the hepatic function, the greater the normal per- 
centage of urea excreted; therefore, excessive uric acid 
excretion in the urine of man is due, in some measure, to 
faulty action of the liver, — less uric acid being destroyed 
(oxidized into urea) than the perfectly healthy liver is 
capable of. 

In the human species, the possibilities of a given organ 
evolving to a higher stage, is seen in the greater number of 
convolutions in the highly intellectual brain as compared 
with the brain of persons in a lower stage of civilization. 
The one is capable of greater work than the other. As 
we add to the sum of our knowledge concerning the influ- 
ence upon the liver of certain foods ingested, we may 



PURIN METABOLISM. 55 

eventually learn to eat such substances (both as to quan- 
tity and quality) as tend to develop and aid the hepatic 
function, rather than those that injure this important 
metabolic process. An equally beneficial effect upon the 
other tissues will naturally follow. 

Future generations of man, there may be in existence, 
whose metabolic power (like brain power) will have be- 
come developed to such a degree that all nitrogenous 
waste will be fully oxidized into its end product, urea; 
and such intermediary products as uric acid and allantoin 
will disappear from the urine entirely. Such an improve- 
ment, at all events, would be in the line of evolutionary 
growth and development. 

If human flesh were to be utilized as food, it is evident 
that uric acid itself, as well as the "free" xanthins, would 
be found in the blood and tissue juices of the meat and 
glandular organs thus ingested. In the carnivorous and 
omnivorous flesh food now eaten, such as fish and pork, 
as well as in all herbivorous flesh food, we obtain only the 
purins oxidized to a stage short of uric acid; thus demon- 
strating the fact that the intracellular ferments of these 
animals have not yet reached the more fully evolved form 
of those present in human cells, which are capable of 
further oxidizing these "free" purins, not only into uric 
acid, but, in some instances, into urea itself. 

It is a mooted question, and open to wide speculation 
and theorizing, as to the exact chemical form in which 
uric^acid would be found in healthy human flesh food, 
i. e., in the blood and extra vascular fluids; whether as a 
salt or in loose combination with some organic atom com- 
plex, and in what physical form. But, doubtless, much 
would depend on the particular locality in which it was 



56 URIC ACID AND ITS CONGENERS. 

found. If in the lymph spaces before combining with the 
soda salts of the blood, it would perhaps be in a form like 
other "free purins"; if in the capillary blood, it would 
probably be in the form of a colloid urate of soda; and 
if in the general circulation, it might be less colloid but 
still in the form of a urate. In short, its chemical and 
physical form would probably vary in a similar manner 
to that of the glycocholic acid and glycocholate of soda 
contained in bile, which has also occasionally been found 
in the urine, as a sodium salt. 



CHAPTER VII. 

EVOLUTIONARY DEVELOPMENT. 

The "Special Creation" Theory. — To account 
for the various animal forms about us, the "special crea- 
tion" theory has long offered to the superficial observer 
the only satisfactory explanation. The human mind, in 
its partially developed stage of enlightenment, pictured 
an epoch when the earth was devoid of animal life; when, 
suddenly, by the fiat of a Great Personal Architect, 
myriads of denizens of the air, land, and sea, sprang into 
existence in completed form and shape as we see them 
today. 

The crude thinker seems to be incapable of conceiv- 
ing of a thing created, unless it be done instantaneously 
(or comparatively so), after human methods, — e. g., as a 
tin soldier is created by a toy-maker. By such a mind 
the Deity is thought of as a personality, of the masculine 
gender, who once created living images of himself, and 
is now resting somewhere from the toils of his handiwork, 
— after the manner of the carpenter or sculptor. 

But how lowly a conception is this! Is it any less 
repellent to the pure religious instinct, to conceive of an 
intangible (spiritual) Power, immanent in every atom of 
the cosmos — the Soul of things — which is as active and 
potent today as of yore, in causing an increase in complexity 
of structure and function, to keep pace with the corres- 
ponding changes in the environment, in the great struggle 
for existence ? 

Do we in any way detract from the lofty attributes 
of Omnipotence, in believing that all physical and psychi- 






58 URIC ACID AND ITS CONGENERS. 

cal phenomena are a manifestation of this Omnipotent 
Power, from whence these forces emanated in the begin- 
ning, and are equally pregnant still in gradually giving 
birth to newer from older forms, until we reach the en- 
lightened human being of the present, who is still evolv- 
ing slowly, but surely, to a higher intellectual and ethical 
plane, — i. e., to a mental or spiritual state in which he is 
capable of more nearly appreciating the inherent nature 
of the Creator and the methods of creation ? At all events, 
they conceive of a mere finite Power, who believe that 
man in his present condition represents the climax of his 
Maker's skill. A higher religious faith is that which con- 
strains us to believe that the human mind (rather than 
the human body) is in the likeness of its Maker — the Uni- 
versal Mind, towards the meeting and knowing of Which, 
It is gradually evolving ours. 

The "Spencerian" Theory. — Modern biologists 
and morphologists, who have studied deeply into the 
nature and changes of tissue structure and the correspond- 
ing increase in the complexity of function in the animal 
economy, have been obliged to reject the old "special 
creation'' theory which was clung to so religiously by our 
ancestors; and, in its stead, have accepted the more ra- 
tional belief in a gradual evolutionary development from 
simple to more complex organic forms. 

The universal principle or law of evolution, whose 
working is so plainly seen in the gradual growth and 
development out of barbarism of the modern social life, — 
ever tending to a more complete sociologic organization, — 
is the same, when studied from a biologic viewpoint, in 
its application to individual organic forms. In short, man 
in his present physical, moral and intellectual state and 



EVOLUTIONARY DEVELOPMENT. 59 

form, is not an act of special creation, but, like our modern 
civilization, is a complex product of slow growth, evolved 
from simpler pre-existing forms, seriatim ad infinitum, — 
similar in plan to the development of the human foetus 
from the parent germ cell: the gradual growth and de- 
velopment of which in the mother's womb represents, on 
a small scale, the various stages of human evolution during 
the past ages. 

Evolution of every kind, whether mental, ethical, 
social or physical, is an increase of complexity of structure 
and function, accompanied by a dissipation of motion or 
energy and integration of matter or substance: "A 
change," says Spencer, "from an indefinite incoherent 
homogeneity to a definite coherent heterogeneity." As 
the organism, (of whatsoever nature) grows as a whole, 
its component parts necessarily develop pari passu, during 
which process there is always a survival of the fittest. 

Transitional Stage. — Every man who accepts the 
Spencerian theory of evolution, in its application to physi- 
cal, intellectual, moral and social progress, will readily 
appreciate the fact that the human organism is still in a 
transitional stage of growth and development, — i. e., has 
not yet reached organic perfection. 

Man is recognized as the highest form of animal life 
in existence, chiefly because of his superior intellectual 
capacity, — his power to mold the environment to his will. 
His high position, as compared with the other members of 
the mammalian species, depends not so much on general 
physical attributes, as on the rapidity with which he is 
evolving along psychical lines. We note the same in- 
tellectual superiority of the civilized man over the savage 
and we find that the complexity of structure correspond- 



60 URIC ACID AND ITS CONGENERS. 

ing to this increase in mental function, consists in the 
multiplication of cerebral convolutions as well as in the 
greater mass of cerebral tissue. 

It would seem evident enough to the thoughtful 
observer that the tendency of human evolution is to minim- 
ize or reduce the expenditure of muscular energy, (nec- 
essarily utilized by animals for the purposes of mere 
existence), thus leaving a reserve force to expend toward 
intellectual growth and development. For example, in- 
stead of wasting so much energy in muscular effort to 
procure sufficient food for the body needs, as was the 
custom of yore, the enlightened man of modern times is 
supplied with food with little or no expenditure of muscu- 
lar force on his part, thus affording him opportunity to 
utilize the equivalence of this force in the form of cerebral 
activity. 

Moreover, food is now prepared in such form (owing 
to the art of cooking, etc.), as to require much less ex- 
penditure of energy on the part of the organism to masticate, 
digest and assimilate it for the body needs, thus again 
leaving a reserve force to be utilized for intellectual pur- 
poses. In short, man is evolving along intellectual lines, 
and the cerebral organ and its accessories necessarily 
evolve pan passu. 

As man becomes more intellectual, he may so appor- 
tion out the work to his vegetative organs and involuntary 
tissues that the minimum waste of energy will result. He 
will, at least, see that no unnecessary work is put upon 
them. As he learns that certain so-called food substances 
furnish no nutriment to the organism through which 
latent energy is supplied, but, on the contrary, that they 
require the expenditure of potential energy to insure their 



EVOLUTIONARY DEVELOPMENT. 61 

removal from the system, he will no longer admit their 
ingestion. He will finally learn that no waste should be 
presented to the kidneys for excretion, except only that 
which results from the expenditure of energy essential to 
the needs of the organism, and represents some physiologi- 
cal work performed, — the normal wear and tear of body 
cells. 

The time is near at hand when the highly intellectual 
man will learn to eat only just enough for his needs, and 
just the kind of food he needs. When he has evolved to 
this desirable stage, much unnecessary metabolic work 
which is now being performed by his liver and other tissues 
will be a remembrance of the past. The cells will be given 
an opportunity to become more highly specialized and 
perform their now lighter metabolic duty more satis- 
factorily. In short, under such circumstances, enzymatic 
oxidation will be more thoroughly performed, and inter- 
mediate products of catabolism will gradually disappear 
from the urine. 

In a human organism evolved to the stage under dis- 
cussion, only urea will be excreted as the true end product 
of nitrogenous waste. Uric acid and its congeners (the 
xanthins) will be known only as vestigial curiosities, — 
i. e., so far as the urine is concerned. This fact is well 
illustrated in studying the structure and function of the 
metabolic and excretory organs of oviparous animals, as 
compared with those of mammals. In birds, serpents and 
fowls (whose nitrogenous end product is uric acid), in- 
stead of a fully developed genito-urinary apparatus, with 
kidneys and accessory organs, we see a crude analogue of 
the kidney, (composed of tissue scarcely more highly 
specialized than muscle), from whence lead ureters, end- 



62 URIC ACID AND ITS CONGENERS. 

ing in a common cloaca with the rectum, through which 
are excreted both urine and feces. As might be expected, 
the function of tissue structures, evolved only to this inter- 
mediate stage, is correspondingly intermediate in its 
character, — only partially developed, and, instead of the 
completely oxidized, soluble end product of nitrogenous 
catabolism, urea, (which has been evolved pari passu with 
the fully developed kidney of mammals), we find the less 
soluble intermediate waste product, uric acid. In other 
words, the metabolic and excretory organs of oviparous 
animals have not been evolved to that stage of complexity 
of structure, which necessitates corresponding complexity 
of function, in the way of complete enzymatic oxidation. 

The Decimal Decrease. — That the uric acid and 
less completely oxidized purins, which are still found in 
comparatively small amount in the urine of carnivorous 
and omnivorous mammals, may be considered as evi- 
dences of a transitional stage in the catabolism of nitrog- 
enous molecules in the animal economy, will be better 
understood when studying the proportional quantities of 
nitrogen contained in these several intermediate products, 
as compared with that in urea. At least, the gradual 
decrease observed, on a regular decimal scale, would seem 
to possess a peculiar metabolic significance. 

It is well known, for instance, that of the total amount 
of nitrogen normally excreted from the body in the urine 
of man, nine-tenths is contained in urea. Of the remaining 
portion, nine-tenths is contained in uric acid. Of the 
portion which still remains, nine-tenths is contained in the 
other oxypurins, of which nine-tenths is in the form of 
xanthin and one-tenth hypoxanthin. It will be seen, also, 
that the nitrogen contained in the two oxypurins (con- 



EVOLUTIONARY DEVELOPMENT. 63 

sidered together) bears the same decimal ratio to the less 
amount contained in the aminopurins, i. e., nine-tenths 
to one-tenth. 

The point which chiefly attracts attention here is that 
the lessened ratio of nitrogen excretion corresponds with 
the lessened oxidation of the product containing it, as repre- 
sented in urea, uric acid, xanthin, hypoxanthin, etc. In 
short, the more highly oxidized products are excreted in 
greatest amount and contain the most nitrogen. From 
which it would seem fair to infer that the human organism 
is evolving gradually and by regular steps to a more perfect 
stage, in which urea, the complete end product of proteid 
and nuclein metabolism, will be the only excreted waste 
molecule containing the used up nitrogen of the system. 

The aminopurins, xanthins and uric acid appear to 
be slowly disappearing (and in that order), from the urine 
and, eventually, they will be found only in the solids and 
fluids of the interior of the body, where they, of course, are 
formed temporarily during the primary and intermediary 
stages of enzymatic oxidation. As the tissues become 
more highly specialized, the work of oxidation will be more 
thoroughly performed, and only the completed end pro- 
duct (urea) will be presented to the kidneys for final ex- 
cretion. 

That such a desirable stage of cellular metabolism is 
in the line of structural and functional evolution is made 
abundantly manifest from the study of comparative mor- 
phology and physiology in the animal kingdom. As the 
man of the future learns better how he ought to "eat to 
live," cutting out unnecessary purin extractives, etc., from 
his dietary, and curtailing all useless metabolic effort, his 
intracellular ferments will be enabled to perform their 



64 URIC ACID AND ITS CONGENERS. 

lessened work more thoroughly, and enzymatic oxidation 
will be carried to completion. 

An Intermediate Product. — When it was first 
discovered a few years ago that uric acid was not a product 
of pure albumin-metabolism, — i. e., not a half-way stage 
in the formation of urea during albumin-metabolism, — 
many physicians jumped to the erroneous conclusion that 
uric acid, therefore, was not oxidized into urea. Even 
many pure chemists, when they found that uric acid was a 
product of nuclein and muscle-metabolism instead of 
albumin-metabolism, and that these two metabolic pro- 
cesses were carried out along two entirely different lines, 
at once concluded that uric acid was the complete end 
product of nuclein-metabolism, just as urea was the com- 
plete end product of albumin-metabolism. 

This, however, is found to be untrue. It is now well 
known that at least fifty per cent, of the uric acid derived 
from nuclein metabolism is normally oxidized into urea 
before being excreted. One of our most prominent 
physio-chemists is of the opinion that all of the uric acid 
would be thus further oxidized, if the blood containing it 
passed through the liver. He says: "We may hence con- 
clude that the appearance of these bodies (uric acid and 
xanthin bases) in the urine is under normal conditions 
owing to the fact that not all of the blood of the body 
reaches the liver before being carried to the kidneys." 
(Cf. Simon's Physiological Chemistry, page 254.) 

The enzymes or ferments of the general tissues, in 
the present stage of evolution of the human organism, are 
chiefly the nuclease, guanase, adenase, xanthin-oxidase ? 
etc., whose special function is to hydrolyze or oxidize the 
purin radicals during the first stages of nuclein cleavage 



EVOLUTIONARY DEVELOPMENT. 65 

and break-down, carrying on the process seriatim to the 
uric acid stage and, in some instances, to the urea stage, 
— i. e., in those tissues which have become somewhat more 
highly specialized, such as that of which the glandular 
organs are composed. 

The general tissues themselves have not yet been 
evolved to the complexity of structure and function 
observed in the liver, whose glandular cells have become 
so much more highly specialized as to secrete a ferment 
which possesses a higher oxidizing power than the others 
mentioned, being able to carry out the purin (nitrogen- 
ous) metabolism to completion, — as represented in the 
urea molecule. Doubtless the time will come, however, 
when there will be intracellular ferments of similar en- 
zymatic power, and the oxidation of the nitrogenous mole- 
cules, resulting from nuclear destruction in their immedi- 
ate vicinity, will be carried to the end stage (without the 
essential aid of the liver ferment), when there will then be 
excreted from the body only the fully oxidized waste pro- 
duct of all nitrogenous metabolism (both nuclear and al- 
buminous) in the soluble form of urea. 

Such intermediate and partially oxidized nitrogenous 
products, as the purins and ureids — which are more 
difficultly dialyzed than urea by the delicate and highly 
evolved rodded epithelial cells of the renal tubules — 
will eventually disappear from the urine of man, except- 
ing under abnormal conditions. While this is a mere 
theory, yet, even now, we know that fully one-half of the 
uric acid normally excreted may be made to disappear 
simply by putting our knowledge into practical use, in 
the selection of purin-free food substances. We know, 
too, that much more purin waste will be oxidized into urea 



66 URIC ACID AND ITS CONGENERS. 

if we do not cripple the action of the liver oxidase by 
ingesting alcohol, or otherwise injuring the hepatic func- 
tion. 

Muscle Metabolism. — Until very recently, it has 
been thought that the endogenous purins were derived 
principally from the nuclein of the disintegrating tissue 
cells of the body. But it is shown from the highly inter- 
esting experiments of Burian that this can hardly be true, 
that much of the uric acid normally excreted is, in fact, 
derived from the hypoxanthin which is being constantly 
formed by muscle metabolism. Whether muscle is in a 
state of rest or activity, hypoxanthin is formed to a greater 
or less extent, and this is transformed by the hypoxanthin- 
oxidase of muscle into uric acid and some of the latter is 
further oxidized into urea by the oxidases of the liver. 

As muscular activity results in an increase of the pro- 
duction of muscle-hypoxanthin, and consequently of uric 
acid, it will be seen that more uric acid is now developed in 
the human organism than will be the case in the more 
highly evolved and intellectual individual of the future, of 
whom less muscular energy will be required for the body 
needs. This is but another of the indications that point 
toward the gradual disappearance of uric acid and its 
congeners from human urine, — i. e., as judged from the 
evolutionary standpoint. 

Without these findings of Burian, however, it ought 
to have been known a priori that only a part of the endog- 
enous uric acid, formed in the body, could possibly be 
derived from the destruction of tissue cells. The six or 
eight grains of endogenous purin contained in the twenty- 
four hours' urine, indicate the actual formation in the body 
of twice that quantity, or fifteen grains, — since fifty per 



EVOLUTIONARY DEVELOPMENT. 67 

cent, was doubtless oxidized into urea. For such an 
amount as this, at least six ounces of nuclein would have 
to undergo destruction and this, as may readily be under- 
stood, is an enormous daily cell destruction. " Cells are 
too valuable to the organism," as one author correctly 
says, "to be so lavishly destroyed." 

It is now becoming the generally accepted belief 
among physiologists, that the endogenous purins excreted 
from the body are derived principally from muscle meta- 
bolism, rather than from cellular catabolism (or nuclein 
break-down). Such, indeed, is the opinion of such well- 
known investigators as Burian, Chittenden, Mendel, 
Macleod, and others. 

Vis Inertice. — It is well known that the proteids of 
the tissue and nucleins of the cells, which are so essential 
to the structure of the human organism and to all animal 
life, differ from the other molecular compounds because 
of the nitrogen contained in the former, which is peculiar 
to all albuminous matter. 

It is also known that these proteid and nuclein mole- 
cules are very unstable and constantly being broken down 
(giving off heat, motion, electric force, etc.), and the 
nitrogen discharged from the body in the simpler molecules 
of CHNO, which compose urea, uric acid and the purin 
bases. In health, therefore, a certain amount of nitrogen 
(three drams, by weight) is being eliminated daily by 
way of the urine : now combined in a molecular com- 
bination in which there is no " explosive" action, the 
latter being lost when heat and energy were liberated at 
the moment of the breaking up of the proteid or nuclein 
molecule — just as the nitrogen of gunpowder, or the nitro- 
glycerine of the bomb shell, has lost activity after the 
"explosion" has taken place. 



CHAPTER VIII. 

ACCUMULATION IN THE ORGANISM. 

Purin Removal. — Unlike fat and the glycogen of 
carbohydrates, nitrogenous extractives are not stored 
up for future use in the body. Especially is this true of the 
purin intermediary and end products. As the ash of 
burned up tissue material, they can serve no further 
possible purpose in the animal economy; consequently, 
the sooner they are removed the better. Their retention, 
as such, in the human organism, is anomalous: they 
belong to the non-living part of the material world, to which 
they are to be restored, there to be taken up into vegetable 
tissue, and reorganized into a form of potential energy 
through the kinetic force of the sun's rays. 

Normal Findings of Uric Acid. — A certain amount 
of uric acid is necessarily always present in the body, 
owing to the constant breaking down and death of worn 
out tissue cells, and the ingestion of purin containing 
foods from which it is derived; but it should never 
remain at rest in any particular locality,— normally, it is 
always moving. 

In the healthy human organism, therefore, uric acid 
will be found either (i) in the lymph or blood plasma, 
bathing a given tissue or organ, where it is just leaving 
the dying cell and starting out on its journey of exit from 
the body; or, (2) at some point in the general circulation 
where it is proceeding on its way out. From the moment 
of its birth, it has but one legitimate object in view, and 
that is to reach the outer world and rid the organism of its 



ACCUMULATION IN THE ORGANISM. 69 

presence; for it can be of no further use in the schema of 
life until it reaches the non-organized world. 

Its Presence a Menace. — The presence of uric 
acid in the animal body (even physiologically speaking) 
is a constant menace, for three reasons; viz.: I. It draws 
upon an essential salt constituent of the blood (sodium) to 
enable it to be moved along in that menstruum. 2. Much 
of it, (especially the exogenous portion), calls for the 
expenditure of energy on the part of an important organ 
(the liver) to oxidize it into a more soluble end product 
(urea), and thus further its passage through the blood and 
present nitrogenous waste to the kidney in a more suitable 
form for final excretion. 3. Like any foreign colloid, it is 
liable to get in the way and serve as an impediment. 

Toxicity of the Purins. — The question may well 
be asked, that, if uric acid is so much of a menace, why 
does nature go to the trouble of forming it from the xan- 
thins ? Why not let the xanthins remain as the unoxidized 
end product of nuclein metabolism ? Perhaps the answer 
is to be found in the fact that, though the xanthins may 
not be troublesome for the reasons given above, they are 
even a greater menace than uric acid itself, and for an 
entirely different reason, — i. e., some of them are distinctly 
toxic. It has been demonstrated that the daily injection 
of hypoxanthin into rabbits for two months, results in the 
appearance of distinct degenerative changes in the liver 
and alterations in the constituents of the bone marrow- 

From the reports of several competent experimenters, 
notably those of Gaucher, Tandler, Kolisch, Dostal and 
Croftan, it has been shown that lesions of the renal cells 
and arterioles have been produced by the injection of purin 
bodies into the tissues of animals. In short, we have 



70 URIC ACID AND ITS CONGENERS. 

learned that the xanthins are capable of producing patho- 
logic changes and giving rise to clinical symptoms similar 
to those of poisoning by ammonia. It is well known to 
chemists that uric acid is a substance more difficult to 
decompose than are the xanthins. Therefore, in the form 
of uric acid, the nitrogen or ammonia, which the body 
wishes to excrete, is less likely to be liberated from its 
holding and set free in the organism. As an end (or inter- 
mediary) product of purin metabolism, it will be seen that 
the nitrogen is held more firmly in place in the stable uric 
acid molecule than in that of the more soluble, but less 
stable, xanthins. 

Why Not Urea ? — Again, it may be asked, why is 
not all of the uric acid decomposed into urea ?— thus> 
avoiding the constant menace due to the presence of the 
former substance. Perhaps it would be thus decomposed 
if all of it passed through the healthy liver. In our present 
stage of evolutionary development, the individual tissues 
are not sufficiently specialized, as yet, to perform this 
oxidizing function, except in part. Some time in the 
distant future, there may be members of the mammalian 
species in existence, who will know of uric acid and look 
back upon it only as a vestigial curiosity. The fact that it 
withdraws an essential alkaline constituent from the 
blood (sodium) to enable it to be removed from the body, 
shows the need of evolutionary improvement. 

Uric Acid Excess. — The frequent accumulation of 
uric acid in the body is a well-established fact. To explain 
this phenomenon, theories galore have been offered by 
different investigators. Reasoning a priori, the presence of 
an excessive amount of uric acid in the body at any time 
might be attributed to one of several causes, or to the 
action of two or more of such causes combined, to wit: 



ACCUMULATION IN THE ORGANISM. 71 

1. To hyperactivity of cellular energy throughout the 
body, or in some certain locality, leading to greater cell 
destruction and consequent increased nuclein metabolism, 
thus resulting in increased production of uric acid from 
oxidation of the superabundant xanthin cleavage products. 

2. To inability on the part of the kidneys to eliminate 
the quantity of urates ordinarily brought to them for 
excretion, thus resulting in a direct retention of uric acid in 
the system. 

3. Owing to deficient oxygenation, or for some other 
reason, the individual tissues, and particularly the liver, 
may fail to decompose their accustomed quota of uric acid 
into urea, thus leading to an abnormal quantity of unoxi- 
dized uric acid being left in the circulation on its journey of 
exit. 

4. To some change or changes in the character or 
composition of the blood, due to internal or external causes, 
which tends to prevent uric acid from forming its usual 
soluble combination to enable it to be moved along on its 
journey, of exit, thus causing its precipitation out of the 
blood and deposition in the tissues, where it accumulates 
owing to the mutual attraction of its crystals. 

5. To sudden and prolonged exposure of the bodily 
surface to the influence of cold, as in cold baths, leading to 
temporary accumulation of leucocytes in the cutaneous 
circulation, as well as the precipitation of urates in that 
locality, thus causing blocking up of the capillaries and 
consequent retention of uric acid. 

6. To excessive ingestion of purin-containing sub- 
stances, (especially if combined with alcohol), leading to 
oxidation by the liver of less urea, consequently leaving 
more uric acid than can circulate in solution or suspension, 



72 URIC ACID AND ITS CONGENERS. 

thus resulting in the f tiling out of a portion, and its 
deposition around some solid tissue, where it is retained for 
a longer or shorter time. 

7. To long continued failure of the bowel, from one 
cause or another, to eliminate its share of purin waste, 
ultimately resulting in the absorption of the latter into 
the blood, thus (after its oxidation by the liver) increasing 
the amount of circulating uric acid to that extent. 

8. To prolonged violent muscular effort and conse- 
quent overproduction of hypoxanthin, with resulting in- 
crease of uric acid, — more than the kidneys can excrete, if 
long continued. 

In short, it will be seen that the accumulation of uric 
acid in the organism may be due either to increased pro- 
duction, to retention, or to lessened destruction. But, in 
the first and last of these three cases, the quantity of uric 
acid, though greater than normal, may for a time be ex- 
creted by increased effort on the part of the kidneys, aided, 
perhaps, by vicarious action on the part of the skin and 
bowels. 

Purin Foods. — From the feeding experiments of 
Siven, Chittenden, Hall, Taylor and others, it has been 
found that the principal uric acid containing foods are tea, 
coffee, beef-tea, meat juice, meat extracts, liver, thymus, 
kidneys, sweetbread, fish roe, brain, butcher's meat, her- 
ring, peas, beans, asparagus, etc. 

With a normal diet, on which the excretion of uric acid 
was 0.364 grammes, Taylor found that the addition of 
three cups of coffee led to an average excretion of 0.826 
grammes of uric acid per day, i. e., the output of uric acid 
was more than doubled under the influence ofthecaffein 
of the coffee. 



ACCUMULATION IN THE ORGANISM. 73 

Siven's experiments made with diets, from which 
nucleins and free xanthins were practically absent, showed 
very strikingly how variations in the character of the diet 
will change the amount of uric acid. Thus, for a period of 
seventeen days, with a daily diet of potatoes, bread, butter, 
cheese, eggs, milk and apples, the daily output of uric acid 
averaged 0.433 grammes but, when meat was added to 
the diet, the excretion of uric acid amounted to 1.009 
grammes per day. 

It will thus be seen that the continued ingestion of food 
rich in a purin content, may ultimately lead to over- 
exertion on the part of the kidneys, and faulty excretion of 
uric acid, with its consequent retention in the organism. 

Tables of Exogenous Purins. — We submit below 
a conspectus of the tables of food purins, given in the 
"Sixty-eighth Report of the Scientific Grants Committee 
of the British Medical Association," as furnished by I. 
Walker Hall, M.B., Assistant Lecturer in Pathology, 
Owens College, Manchester, England: 

MEATS. 

Undried purins 
Grains per lb. 

Cod 4 . 08 

Plai ce 5-57 

Halibut 7 • x 4 

Salmon 8.16 

Tripe 4.01 

Mutton 6.76 

Veal 8.14 

Pork (Loin) 8-49 

Pork (Neck) 3.50 

Ham (Fat) 8.06 

Beef (Ribs) 7 . 99 



74 URIC ACID AND ITS CONGENERS. 

MEATS. 



Un dried pur ins 
Grains per lb. 



Beef (Sirloin) 9 

Beef (Steak) 14 

Liver 19 

Sweetbread (Thymus) 70 

Chicken 9 

Turkey 8 

Rabbit 6 



46 

27 

43 

°7 
82 

3 1 



VEGETABLES. 

Bread (White) o . oo 

Oatmeal 3 • 46 

Rice ' o . 00 

Peameal 2.54 

Beans (Haricot) 4 • x 7 

Potatoes 0.14 

Onions o . 06 

Tapioca o . oo 

Cabbage (Green) 

Lettuce „ o . 00 

Cauliflower „ 

Asparagus (Cooked) 1.51 

BEVERAGES. 

Grains per pint. 

Lager Beer 1 . 10 

Pale Ale 1 .27 

Porter 1 . 36 

Claret 
Volnay 
Sherry [ 
Port 



t 



The points which will attract attention in these tables 
are the somewhat high alloxur percentages discovered in 



ACCUMULATION IN THE ORGANISM. 75 

beans, oatmeal, peas, asparagus and beers. The presence 
of purin bodies in beer is doubtless due to the "yeasting" 
and the processes of manufacture. Vegetables, other 
than those mentioned, and wines, are found to be free 
from purins. The purin contents of meat extract, coffee 
and tea are not given, but are, of course, known to be 
much higher than any other beverage, or than beefsteak 

itself; to wit: Uric acid and 

Xanthins 
Grains per lb 

Herring (Loch Erne, kippered) 6.40 

Herring (bloater) 2 . 20 

Meat juice 49-7° 

Meat extract 63 . 00 

Tea 175-00 

Coffee 70 . 00 

Cocoa 59-0° 

It is perhaps well to bear in mind that the blood and 
tissue juices of very young veal ("bob-calves"), like that 
of children, contain a ^higher percentage of uric acid than 
older ones, owing to the greater number of leucocytes, and 
to the lesser decomposition of uric acid — -i. e., into urea. 
This is probably owing to the relatively lower degree of 
alkalescence of the Wood,] (and higher urinary acidity), 
caused by an exclusive albuminous or animal diet (milk). 

White vs. Dark Meats. — Concerning the popular 
opinion that white meats are more suitable for the sick, 
owing to their greater digestibility and the supposed pres- 
ence of less uric acid and nitrogenous extractives, it may 
be said that this belief is shaken by the analyses made by 
Opper and Rosenquist, which show that while white 
meats, such as poultry and fish, do in certain cases con- 
tain less purin extractives, yet the average amount does 



76 URIC ACID AND ITS CONGENERS. 

not appreciably differ in dark and white meats, such as 
poultry, veal, beef, pork, mutton, etc., to make either pref- 
erable. They point out that the only way of limiting the 
ingestion of these deleterious uric acid derivatives is by 
diminishing the amount of meat taken, rather than for- 
bidding dark meats. 



CHAPTER IX. 

ACCUMULATION IN THE ORGANISM. 

Continued. 

Blood Alkalescence. — It is a physiological truth, 
the significance of which cannot be overestimated, that 
the vital processes of animal life require for their consum- 
mation a proper alkaline environment. In other words, 
the chemic, physiologic, ionic or electric manifestations 
of force, which we call "the vital processes," are essen- 
tially connected with a certain degree of alkalinity on the 
part of their surroundings, (i. e., the presence of K, Na ? 
etc., "ions"): if this alkalescence be lowered or weak- 
ened to any extent, a condition results favorable to the 
neutralizing action of toxins and other chemic manifesta- 
tions or, "symptoms," which we recognize as disease. 

It is well understood, for instance, that the tissue 
juices and solutions within the body are normally alka- 
line, — the acid gastric juice, perspiration and urine being, 
strictly speaking, excretions, and outside of the true in- 
terior of the body. The alkaline reaction of the blood is 
found to be owing to the presence of mononatrium (or 
alkaline) carbonate and dinatrium (or neutral) phos- 
phate; and, so important has the question of maintaining 
a certain degree of alkalinity come to be considered, in 
its relation to the metabolic processes, that investigators 
are now impelled to believe that any factor which pro- 
duces chemic changes in the composition of the blood and 
body juices, lowering their alkalinity, is one of the primal 
causes and starting points of disease. 



78 URIC ACID AND ITS CONGENERS. 

It is claimed that many of the lower animals (espe- 
cially herbivorae) are more rarely the subjects of infec- 
tious diseases, as compared with man, owing to a higher 
degree of alkalinity of the blood. Von Fodor has demon- 
strated (Cf. Centbl. f. Bakt . u. Prasitkd., 1 894) that the 
organism of rabbits injected with an alkali, manifests a 
greater bactericidal action toward anthrax, and that life 
was preserved longer than in the case of the control ani- 
mals — those not so treated. Burian and other observers 
have found a lessened degree of alkalinity of the blood in 
such affections as cirrhosis of the liver, chronic nephritis, 
chronic rheumatism, gout, malaria, diabetes, tubercu- 
losis, etc. The same holds especially true of leukaemia, 
where the increased production and destruction of the 
leucocytes of the blood are characteristic. 

Urinary Acidity. — The question may well be asked: 
How shall the daily observed phenomenon of an acid 
water flowing from an alkaline reservoir be accounted 
for, — i. e., acid urine from alkaline blood ? Is it a uni- 
versal law that the watery excretion from the blood of 
animals, and containing the worn out ashes and clinkers 
of the system, shall become acid the moment it becomes 
urine ? Evidently not: for it is a well-known fact that only 
the urine of carnivorous and most omnivorous animals 
is acid, while that of all herbivorae is alkaline. It is 
known, too, that an omnivorous animal, like man, may so 
regulate his diet (by partaking principally of vegetable 
foods) as to cause an alkaline or neutral urine. 

The acidity of human urine, then, depends upon the 
presence in the blood of some substance resulting from 
the disintegration of animal foods ingested, — evidently, 
chiefly the nucleins, whose cleavage products are xanthins 



ACCUMULATION IN THE ORGANISM. 79 

and phosphoric acid; for it is known that the acid reac- 
tion of urine is due to the acid phosphate of soda (which 
exists as a neutral phosphate in the blood). When this 
salt is submitted to dialysis, a larger amount of phosphoric 
acid is found on the outside than on the inside of the 
dialyzer, showing that the acid of the salt diffuses faster 
than its base. As a result, acid phosphate appears out- 
side of the renal dialyzer and renders the urine acid, — 
and in this way we get an acid water flowing from alka- 
line blood. 

Weakened Reaction of Blood. — It has been seen 
that the acidity of the urine in a given case depends in 
great measure upon the carnivorous proclivities of the 
individual, especially upon the amount of nucleins in- 
gested with animal foods, the decomposition of which 
within the body results first, in a superabundance of xan- 
thin cleavage products in the blood, and then of uric acid, 
the latter being insoluble in proportion to the degree of 
acidity of the solution. As might be expected, a high 
degree of urinary acidity, a weakened reaction of the 
blood, an'd the presence in the latter of an increased 
amount of uric acid, go hand in hand. All three of these 
conditions have been found to follow excessive nuclein 
feeding. 

That the alkalescence of the blood becomes dimin- 
ished, is doubtless owing to the neutralizing of the 
alkaline carbonates, a part of whose sodium is extracted 
to unite with the uric acid present, to form urates. "As 
a consequence of this transformation, " says Simon (Physio- 
logical Chemistry, 230), "the alkalinity of the blood must 
diminish. But as such a change would give rise to serious 
disturbances, and as there is a strong tendency on the part 



80 URIC ACID AND ITS CONGENERS. 

of the body to maintain the composition of the blood con- 
stant, particularly its alkalinity, — a loss of alkali is 
guarded against by subjecting the various neutral salts to 
the specific activity of the renal epithelial cells;" i. e., as 
a result of the renal dialysis, previously described, that 
portion of the sodium base (of the neutral phosphates) 
left behind, — after the acid part has escaped through the 
dialyzer (renal epithelial cells) into the urine, — is trans- 
formed into alkaline sodium carbonate, which is returned 
to the blood, thus tending to preserve its alkalescence. 

While it is true, therefore, that Nature is constantly 
striving to prevent a weakened reaction on the part of the 
blood, and that, under ordinary circumstances, she will 
doubtless succeed, nevertheless, it can be seen that exces- 
sive nuclein feeding, plus increased nuclear tissue destruc- 
tion throughout the body, and, perhaps, faulty destruction 
of uric acid into urea, may not only lead to urinary hyper- 
acidity, but to subalkalinity of the blood, caused partly by 
abstraction of sodium from the economy in the form of 
urinary urates and phosphates (of sodium), and partly by 
extraction of the alkaline carbonates in the blood itself to 
form sodium urate. In other words, though Nature's 
efforts to preserve an equilibrium may generally prove 
successful; yet, at times, under a stress, they may become 
inadequate, — when a weakened reaction of the blood en- 
sues. 

Deposition of Urates. — As the blood, even with its 
normal alkalinity, is no more than able to just hold the 
urates in solution or suspension, — sufficient to insure their 
transit in circulation, — it is obvious that, during those 
periods of "weakened reaction" referred to, the urates are 
likely to fall out as a deposit, thus resulting in their tem- 
porary accumulation. 



ACCUMULATION IN THE ORGANISM. 81 

The manner in which such deposition may occur is 
probably similar to that already described in a previous 
chapter, when considering the "precipitation" of uric acid 
crystals as observed in vitro. In the form of a "colloidal" 
solution, it is with difficulty that the passage through the 
capillaries is effected, so that partial or complete stasis 
often exists; and a slight reduction in the alkalinity of the 
solution occurring at such times, the urates will doubtless 
crystallize out (as in the laboratory) and become attached 
to the nearest solid tissue structure. Especially will this be 
true, if exposure of the surface vessels to cold happen at this 
time, which, of course, tends to hasten crystallization and 
precipitation. 

Such temporary deposits will be reabsorbed into 
solution, (as in vitro), upon restoral of the proper degree of 
alkalescence to the blood; and the urates may be conducted 
to another locality and there again be deposited, under 
similar conditions: and so on, time after time, the process 
may be repeated. 

Again, it is well known that strain or activity of 
muscle fibers, as during prolonged muscular effort, causes 
increased cell destruction, with production of xanthin 
cleavage products and consequent uric acid; also reduced 
alkalinity of the lymph and blood plasma in that neighbor- 
hood. As may be foreseen, a deposition of urates, as above 
described, will probably occur in this locality under these 
circumstances. 

From what has been said, it will be understood that 
any factor which tends to reduce the normal alkalescence 
of the blood stream is likely to cause precipitation of the 
urates and their deposition and accumulation, especially 
at such points where the circulation is most sluggish (as 



82 URIC ACID AND ITS CONGENERS. 

through the capillaries) and where most exposed to in- 
fluences of cold, or where increased work and cell destruc- 
tion is going on and where the uric acid itself is increased in 
consequence. Even in constipation, where absorption of 
acid juices from the retained fecal mass lowers the blood's 
reaction; or, in dyspepsia, with acid fermentation of un- 
digested food and consequent absorption, — the same 
tendency occurs for the urates to become deposited at some 
point in direct contact with the solid tissue structures where 
the conditions above mentioned are most favorable, and 
where the deposit is likely to accumulate owing to the 
stronger attraction of the crystals en masse. 

Effect of Alcohol. — Some very significant experi- 
ments concerning the effect of alcohol in interfering with 
the oxidation of uric acid derived from its precursors in the 
food, have recently been performed by Beebe and others, 
and reported in the Amer. Jour, of Physiol., Sept. I, 1904, 
The authors of the experiments have shown that a greatly 
increased quantity of uric acid in circulation follows the 
ingestion of alcohol taken with purin foods; which in- 
crease is attributed to the impaired oxidative powers of the 
liver. In short, it has been demonstrated that alcohol does 
not hasten the excretion of urates already present in the 
blood, but that it interferes with purin metabolism, (oxi- 
dation of uric acid into urea), by its toxic action upon the 
liver, thus resulting in an increased quantity of unoxidized 
uric acid in the circulation, — which necessitates extra 
excretory work on the part of the kidneys. 

No accumulation would occur under these circum- 
stances, provided the kidneys were always equal to the 
emergency of properly excreting the increased quantity of 
urates; but, if the ingestion of alcohol be continued, the 



ACCUMULATION IN THE ORGANISM. 83 

extra eliminative efforts will finally result in renal inade- 
quacy and consequent retention. In fact, von Noorden 
blames alcohol with causing uric acid to be eliminated with 
difficulty, resulting in retention; and he advises in favor 
of aiding uric acid elimination. 

In conclusion, it may be said that, though alcohol is, 
perhaps, a food, in the sense that when used in small 
quantity the energy from its oxidation may be utilized for 
some of the body needs, yet, at the same time, as it inter- 
feres with the normal activities of a most important organ, 
the liver, its food value is counterbalanced by its toxic 
effect; and, as a result, a considerable amount of uric acid 
is left behind in the circulation, unoxidized, — not decom- 
posed into urea in the proportion (50 per cent.) it should be. 



CHAPTER X. 

DISEASE PROCESSES. 

Purin Excess. — The accumulation of an excess of 
uric acid and its congeners in the system, no matter from 
what one or more of the several causes previously mentioned, 
almost invariably gives rise to certain well-recognized 
subjective and clinical signs, which may vary, of course, 
according to the nature of the accumulation and its 
locality. 

Owing to a faulty nosology, our present text-hooks are 
burdened with as many different "names" of disease as 
there are tissues affected ; but from an aetiological viewpoint, 
the disease processes arising from an accumulation of the 
nitrogenous purins and ureids in the system, may all be 
classed under the general head of "Purin Excess." By 
this term, we mean to embrace all disorders resulting from 
the presence in the human economy of an abnormal quan- 
tity (or quality) of uric acid and its derivatives, whether 
suspended in the blood and extra-vascular fluids, or de- 
posited in the various tissue structures of the body. 

Its Three Stages. — Like syphilis, which is arbi- 
trarily divided, as to point of time and location of 
tissues involved, into a primary, secondary and tertiary 
stage, so may uric acid or purin excess be divided into three 
similar stages, viz.: I. Uricacidaemic; 2. Rheumatic; 3. 
Gouty. In the first stage, the urates are still confined to the 
blood; in the second they are deposited in the skin, 
mucosa, or stroma of muscular and glandular tissue, chiefly 
yet in colloid form; in the third, the deposits have reached 



DISEASE PROCESSES. 85 

the deeper, less vascular structures, where they have be- 
come crystalline. 

The line of demarcation is not always sharply drawn 
here, any more than in syphilis, or in pneumonia (con- 
gestion, inflammation, hepatization), where one stage may 
merge into another, or, perhaps, one of them be apparently 
slighted or skipped over. But, as a rule, in a typical case 
of uric acid accumulation, we observe first the symptoms 
due to its presence in excess in the blood, (headache, in- 
somnia, etc.) ; then, of its deposition from the blood into 
the surrounding tissues, where it may be reabsorbed and re- 
moved to some other locality, (muscular pains, etc.); and 
finally, of its retention and crystallization in the terminal 
joints, or deeper structures of low vascularity, (concre- 
tions, etc.). 

Of course, like syphilis, the disease process may never 
reach the third stage, and possibly not the second; but, 
if permitted to go on, the tendency of uricacidaemia is to 
develop into a rheumatic condition and finally gout. On 
the other hand, the symptoms of the primary or secondary 
stage may themselves be overlooked or disregarded, and 
the first complaint to the doctor be made at the gouty stage. 

(i) URICACIDtEMIC stage. 

Names. — The terms " uricacid-aemia," " purin-aemia," 
"uric-aemia" and "lith-aemia," as suggested by their com- 
mon Greek derivative ending ("aemia," or blood), mean 
respectively uric acid blood, purin blood, uric blood, and 
lithic blood. In short, they are equivalent terms used to 
designate the primary stage of "Purin Excess," in which 
the circulation at some point contains so much uric acid, 



86 URIC ACID AND ITS CONGENERS. 

or uric acid in such form, that it cannot be properly con- 
veyed along on its journey of exit from the body. 

Increased Viscosity. — The investigations of Rom- 
berg have taught us that the blood-stream may vary fully 
ten per cent, in viscosity, by changes in its reaction: being 
rendered less viscous when the alkalinity is raised by the 
administration of an alkaline agent like potassium iodide; 
and more viscous when the alkalinity is diminished in any 
way, as by the administration of an acid. As we know 
from clinical experience that one of the chief symptoms of 
the uricacidaemic stage is a sluggish flow of blood through 
the capillaries, and that the alkalinity of the blood is 
diminished at such times, as shown by the accompanying 
urinary hyperacidity, it is fair to infer that the viscosity of 
the blood has also been materially increased by the pres- 
ence of an excess of urates in colloid form. 

Capillary Obstruction. — The clinician knows that 
the principal trouble arising from an accumulation of the 
urates at any point, is owing to its serving as a mechanical 
impediment to a free capillary circulation. He has learned 
from experience that blocking up of the capillaries is 
characteristic of uricacidaemia, and that one of the chief 
objective signs is a scant, high-colored, strongly acid urine 
of high specific gravity, which is, in itself, indicative of an 
impeded capillary flow through the renal epithelial cells. 

The capillaries, of course, serve the double purpose of 
supply tubes and waste pipes. In the latter capacity they 
are obliged to conduct away from a given tissue, the purin 
waste products resulting from cellular activity and cell 
destruction. If the conduits be obstructed, as in the 
uricacidaemic stage, the inevitable result is stasis, con- 
gestion, and, perhaps, inflammation of the particular 
tissue or organ where such stasis occurs. 



DISEASE PROCESSES. 87 

Localization of Symptoms. — It will readily be 
understood that the capillary obstruction, with its result- 
ing congestion in these cases, is most likely to occur in 
those organs or tissues which are called upon to do un- 
usual service, thus throwing an extra amount of labor on 
the capillaries in that vicinity, which, as supply tubes, 
must bring the added nutriment required, and, as waste 
pipes, remove the increased debris (xanthin and uric 
acid) which necessarily results. 

The part to be affected, therefore, when the circula- 
tion is impeded with colloid urates, will vary in different 
individuals, depending on their vocation, — i. e., which 
part of the organism, in a given case, is called upon for 
special effort. The man who uses his brain, or whose 
cerebral capillaries are required to do extra work, will be 
subject to headache, depression of spirits, "fits of blues," 
sleeplessness, inaptitude for mental effort, loss of mem- 
ory, etc. The man of brawn, or he whose muscles are 
constantly engaged, will complain of sluggishness, muscu- 
lar inertia, that "tired feeling," inaptitude for physical 
exertion, etc. In both of these cases the sensory manifes- 
tations, or "symptoms," are doubtless due, in part, to the 
mechanical pressure of the distended venules and arter- 
ioles on the accompanying nerve-fibrillae and their end- 
ings; and, in part, to the direct chemical action or toxae- 
mic effects of the alloxuric bases. 

Faulty Metabolism. — In nearly all cases, in the 
uricacidaemic stage, the liver becomes more or less affected, 
since this organ is actively engaged in every individual; 
and, if its capillary supply or waste be blocked, its func- 
tional activity will be correspondingly lessened or interfered 
with. While it is true that all of the tissue cells of the 



88 URIC ACID AND ITS CONGENERS. 

animal economy take part in the general metabolic pro- 
cess, yet, inasmuch as the liver is the largest and most 
complex organ of the body, containing the greatest con- 
glomeration of such cells, it is not surprising that the 
greatest stress should be laid upon its action, and that 
stasis in its immediate vicinity should finally result in 
so-called hepatic "torpor" and its disagreeable general 
consequences, — i. e., faulty metabolism throughout the en- 
tire organism. 

Capillary obstruction, in this way, may eventuate in 
an "ill burning" fire, in which the purin ashes of nitrog- 
enous combustion (xanthin and uric acid) are retained, 
and accumulate to cause further obstruction, — thus tend- 
ing to form a circulus vttiosus. 

(2) RHEUMATIC STAGE. 

Names. — As may be observed from its Greek de- 
rivatives, the term "rheum-atism," (meaning liability to 
"rheum," or "flux"), was applied originally to a humoral 
malady. In more recent times the term has been used 
synonymously with "arthritism," although the fact has 
generally been recognized that other tissues than the 
joints may be affected. The term "rheumatic," as used 
by us, is meant to designate the second stage of " Purin 
Excess," in which the urates at one or more points have 
been thrown out of solution and deposited in the sur- 
rounding tissues. 

Transition Period. — The change from the uric- 
acidaemic to the rheumatic stage may be gradual or abrupt. 
At any given point, where the capillary flow is more or less 
impeded by accumulation of urates, the deposition into 
the adjacent tissues will be hastened if the latter undergo 



DISEASE PROCESSES. 89 

a sudden strain, or be called upon for work, or if exposed 
to cold, — in all of which cases the alkalinity of the solu- 
tion at that point is lowered, and the urates precipitated 
in consequence. 

In like manner, the deposition into the tissues may be 
hastened by the sudden absorption into the circulation of 
lactic, butyric, et al., acids, caused by gastro-intestinal 
fermentation. The same effect may be produced in the 
uricacidaemic patient, at will, by administering drugs 
which diminish the alkalescence of the blood, such as acid 
phosphate, morphin, antifebrin, etc. Every physician, 
long in practice, has doubtless observed "rheumatic" 
symptoms follow the use of some antipyretic or analgesic 
agent, which was given by him to relieve a severe head- 
ache; or from the use of a hypnotic, such as sulfonal, to 
relieve insomnia. 

Localization of Symptoms. — Like the sensory 
manifestations of the uricacidaemic stage, the subjective 
and objective signs of the rheumatic stage, in so far as 
their character and localization are concerned, will depend 
upon the particular tissues that may be involved, which, 
in turn, will depend in great measure upon the vocation of 
the individual. For instance, the man whose muscles are 
exposed to strain, or to influence of cold, will be subject to 
the muscular stiffness or aches and pains caused by 
deposition of the urates in the stroma or between the fibers 
of the muscles so engaged or exposed. 

Again, if the deposits are in the nerve sheaths, neural- 
gic twinges will appear; if in the mucous membranes, 
catarrhal conditions will supervene; if in the skin, some 
form of eczematous eruption; if in the stroma, or con- 
nective tissue of glands, cirrhosis of the organ, par- 



90 URIC ACID AND ITS CONGENERS. 

enchymatous, or, perhaps, interstitial inflammation; .if 
in the fibrous tissue of the cardiac valves, endo-carditis 
or mitral insufficiency; if in the supporting structures of 
the larger joints, arthritis; if in the intestinal coat, colicky 
pains or sluggish peristalsis; if in the alveolar tissue or 
gums, gingivitis, etc. 

The uratic deposits, in these cases, are probably still 
in the colloid, amorphous, or semi-crystalline form, and 
may be reabsorbed from time to time, to be conveyed to 
some other locality or excreted from the body entirely. 
In the latter eventuality, coincidently with disappearance 
of the symptoms, an increased elimination of urates occurs, 
as may be observed by examination of the urine. 

(3) GOUTY STAGE. 

Definition. — Gout is the third and last stage of 
'Purin Excess. " In the two conditions already described, 
the urates have merely reached the colloid form, remaining 
(1) in the blood as such, or (2) precipitated temporarily 
out into the tissues. In gout, however, the deposits (as 
in the small joints) have finally become crystalline, where 
they oftentimes remain to cause irritation and set up in- 
flammation. 

Formative Period. — Like the tertiary stage of 
syphilis, the gouty stage of "Purin Excess" may be long in 
making its appearance; or, it may fail to appear at all, 
for Nature will endeavor to prevent her waste deposits 
remaining long in the system. It is only when her efforts 
to preserve an equilibrium have been weakened by con- 
stant demand or neutralized by sudden unusual require- 
ments, that the conditions become favorable for the forma- 



DISEASE PROCESSES. 91 

tion of crystalline deposits; and, even then, only certain 
localities are eligible sites for the tophi. 

Repeated slight fluctuations (from lower to normal) 
in the reaction of the body fluids, incident to the accumu- 
lation and removal of uratic waste, may be considered a 
fair measure of the strain that has been put upon the renal 
dialyzer, — to whose proper working the blood looks for 
the restoral of alkali on one side and the elimination of 
urates on the other. Constant use and frequent abuse, in 
this way, may ultimately weaken the selective and dialyz- 
ing function of the renal epithelial cells to such an extent 
as to result in lowered alkalescence of the blood and re- 
tention of urates, — the latter even being precipitated at 
times in the kidneys themselves. 

As may be seen, the chief exciting ^etiological factors 
during the formative period are those which favor the 
accumulation of uric acid, as an excessive ingestion of 
purin containing foods with alcohol, and faulty elimina- 
tion. 

Localization of Deposits. — While the circulation 
of the entire organism becomes thus tainted to a greater or 
less extent on occasions, it is only in distal parts, poorly 
vascularized, where the removal of deposits is delayed and 
where the environing conditions are favorable to the pre- 
cipitation and crystallization of uric acid, that the tophi or 
concretions are formed. We know from laboratory ex- 
periments, as referred to in our previous section on "Crys- 
tallization, " and from the recent investigations of Prof. 
Klemperer (Cf. Therapie d. Gegenwart, May, 1904) that 
a very weak alkaline solution of inorganic salts will dissolve 
uratic deposits, while the urates in the same solution, when 
slightly acidulated, will, on the contrary, be abstracted 



92 URIC ACID AND ITS CONGENERS. 

from the solution to become deposited in crystalline form 
on some contiguous solid substance. 

The four factors which conduce toward the crystalli- 
zation in the organism of uric acid, when its urates are 
present in a saturated or nearly saturated solution with 
other salts, are: I. Repeated sudden dealkalizations of 
the solution due to the fluctuating changes in the quantity 
of its contained alkaline salts; 2. Stasis (complete or 
almost complete) for ten or twelve hours; 3. Low tem- 
perature; 4. An adjacent solid. These conditions are not 
met with in the circulating blood: nor in the blood at all, 
until it is removed from the body, acidulated, and allowed 
to stand and cool, when a solid substance introduced 
becomes the site of crystalline formation, — as in Garrod's 
" thread test." Nor are they met with in the urine itself, 
until it is outside of the dialyzer, at rest in the renal pelvis 
or bladder, and some foreign particle presents as a nidus 
for the formation of calculi. 

The four favoring factors are present, however, in 
certain regions of the body far removed from the cardiac- 
center, exposed to cold (freezing easily), as in the helix of 
the ear and the septum of the nose, and where pressure or 
constriction is put upon the return circulation, as in the 
bursae of certain joints and toward the end of the great 
toe. In this metatarsophalangeal joint, the synovial fluid 
is practically at a standstill, especially when the shoe is on. 
It has been shown by Frerichs that the synovial fluid of 
an animal at rest contains twenty per cent, more of the 
alkaline salts than when in exercise, thus causing sudden 
lowering of alkalinity on motion of the parts, favoring the 
precipitation and crystallization of its contained urates, 
dialyzed from the surrounding capillaries in which the 
colloid urates are present in excess. 



DISEASE PROCESSES. 93 

So long as a blood, rich in urates, is brought to the 
spot., the tophus steadily grows by attracting other urates 
to it. Doubtless there will be alternate precipitations and 
absorptions, keeping pace with the fluctuations in the 
reaction of the synovial fluid. Especially will this be 
observed at night, in the wintry season, after removal of 
the shoe and restoral of the circulation, with rest of the 
parts from motion and warming of the toe in bed. On 
such occasions, either (i) the mechanical irritation of the 
crystals, as withdrawn in part from their site and re- 
absorbed into the now highly alkaline synovia, or (2) the 
chemical effect produced by the change from one form to 
the other,- — may set up congestion and inflammation of 
the surrounding tissues, thus giving rise to an acute 
"gouty attack." 

To account for the well-known predilection of the 
urates for the joint of the great toe, Wakefield, (Cf. Ameri- 
can Medicine, March 25, 1905), offers the following ex- 
planation: 

"Having already referred to the predisposition of 
subkatabolism for certain joints, it only remains to explain 
here why gout predisposes to the metatarsophalangeal 
articulation, and analyze the attack: 1. The great toe is 
the one of greatest strain when walking, and being the 
farthest removed from the heart, and hence most affected 
by splanchnic venous stasis, as well as all of the vascular 
obstructions, arterial and venous, of the intermediate 
tissues, the oxygenation is poorest. 2. The involved areas, 
by flaccid expansion and gelatinous spongy consistence 
becomes extremely prone to impregnation with liberated 
bases. 3. During the period of greatest subkatabolism in 
the twenty-four hours ; during the equilibrium of blood distri- 



94 URIC ACID AND ITS CONGENERS. 

bution, namely, the very early morning hours, uric acid 
salts are taken into solution by the blood and are carried to 
the seat of greatest subkatabolism, there to be englobed by 
jellified tissue. The fact that throughout the vascular 
system the urates are colloidated so completely with 
colloid food and tissue detritus floating in the blood 
current, suggests a possible affinity between the two/' 



CHAPTER XL 

(i). URICACIDiEMIC MANIFESTATIONS. 

Pain. — The intelligence immanent throughout the 
cosmos is nowhere more strikingly manifested than in 
those retributive acts of justice, observed in the human 
organism, (as "remorse") when the subjective center is 
made to suffer for wrongs inflicted on the helpless, in- 
voluntary tissues, — i. e., when notice is given that some- 
thing is wrong in a certain locality, as evidenced by the 
exaggerated sensory impression or perception, which we 
pain. 

The essence of this disagreeable sensation lies in the 
intensity of the stimulus, in the disturbance of the organi- 
zation of the nerve at some point in its course, or in the 
excitability of the sensorium. In either case it is an indi- 
cation that a law of Nature has been violated; and, in 
order that a similar offense may not occur again, a punish- 
ment is inflicted which will tend to deter the subject from 
repeating it. 

The sensation of "fatigue" is only a lesser degree of 
pain. It is localized in, or referred to a certain muscle or 
set of muscles, after prolonged or violent exercise of the 
same. Why ? Doubtless because of the abnormal amount 
of waste present, resulting from the increased disinte- 
gration and death of the cells engaged in furnishing the 
requisite energy; for we know that the sensation gradually 
disappears as the purin waste products are removed by the 
capillaries. In short, we see that the presence of organic 
non-living matter, in excess of the normal, operates like 



96 URIC ACID AND ITS CONGENERS. 

any other foreign body; and notice is given of its presence 
and the necessity for its removal. 

"Pain," in other words, is often but a notification to 
the center of volition of the presence of some abnormal 
material (or normal material in abnormal amount) in con- 
tact with nerve tissue, which, either by mere physical 
pressure, or by some chemical change induced, gives rise 
to the subjective feeling. In all cases, it is an unmistakable 
notice given to the subject that something in that locality 
is present that ought to be removed, whether a mote in the 
eye, a thorn in the flesh, a stone in the bladder, a tight shoe, 
a distended gut or bloodvessel, or what not. As intelligent 
beings, capable of molding our environment, we are sup- 
posed to learn from personal experience, or from the 
experience of others, the nature and cause of the " law- 
breaking " in each instance, — i. e., learn not only how to 
avoid infringement in the future, but how to apply the 
present remedy. 

Headache. — One of the commonest manifestations 
of the accumulation of purin waste — its presence in excess 
in the circulating medium, resulting in capillary ob- 
struction — is the cerebral pain, called "headache" or 
"migraine," due to distension of the cerebral veinlets and 
arterioles, causing pressure on the surrounding nerve 
tissue. 

The conservative headache of menstruation is closely 
connected with uric acid accumulation. We know that 
two or three days prior to the menstrual discharge, there is 
a marked diminution of the urinary excretion of urates, 
which is not accounted for by the presence of an increased 
amount of purin nitrogen in the urine in other forms, for 
the latter remains unchanged, or even diminished. We 



URICACID^EMIC MANIFESTATIONS. 97 

know positively that uric acid is retained in the circulation 
until the second or third day of the flow, when it is excreted 
in greatly increased amount, at the same time of the dis- 
appearance of the headache. The relation of cause and 
effect here, is too close and constant to be disregarded. 

It should be understood that the above is what hap- 
pens in normal conditions, when the organs of elimination 
are active and perform their added duty on such occasions 
properly, — the only symptoms indicative of this temporary 
retention being a slight headache and depression of spirits 
at the beginning of the periods. But, if elimination is im- 
perfect, (as is so often the case), uric acid remains to 
accumulate, and we have all the disagreeable symptoms 
characteristic of migraine. 

As in menstruation, so it is in the regular paroxysmal 
headache of migraine, the greatest excretion of uric acid 
occurs two to four hours after the height of the attack, — 
i. e., occurs as the headache is passing off. One or two 
investigators, notably Lichty, some five or six years ago, 
advanced the idea that this was a proof that uric acid is the 
result of the headache, not the cause. But it would be just 
as rational to say that the excreted uratic calculus or gravel 
is the result of the renal or ureteral colic, instead of the 
cause. 

"Next Morning" Headache. — One of the charac- 
teristic headaches of purin excess, is that which ensues 
"next morning," after an alcoholic debauch. As already 
stated in a previous chapter, the effect of toxic doses of 
alcohol is to interfere with the oxidative function of the 
liver — i. e., inhibit the catalytic action of its ferment in 
decomposing uric acid into urea, thus leaving an abnormal 
amount of unoxidized uric acid in the circulation. Until 



98 URIC ACID AND ITS CONGENERS. 

the organs of elimination succeed in removing this excess, 
the effects of its presence will be felt, especially a few hours 
after ingestion of the alcohol, — at the height of the " alka- 
line tide," during the morning hours, when the uratic 
waste is en route through the organism. 

Previously, as the immediate effect of the alcohol, the 
blood's alkalescence is lowered and the urates precipitated 
out into the tissues, thus leaving the capillary vessels tem- 
porarily open and free, causing a sudden blaze of the meta- 
bolic fires, with the concomitant stimulation and feeling of 
buoyancy. But on the restoral of its normal degree of alka- 
line reaction, the blood reabsorbs from the tissues the 
deposited urates en masse, and we get the disagreeable 
manifestations of their presence, until Nature's conserva- 
tive "explosion" occurs, when, figuratively speaking, both 
the headache and the urates are carried off in the urine, as 
shown by urinalysis. 

Fits of Blues. — As the dark cloud presages the near 
approach of a summer shower, so do the "blues" give 
evidence of a coming "uric acid storm." In one instance, 
the air about us is electrically charged, in the other, the 
blood within us is uratically charged; and a feeling of 
weight or depression precedes the "explosion" in both 
cases. 

A fit of the blues is felt just as the storm is brewing, 
just as the accumulation is beginning to impede the capil- 
lary flow, which will soon reach the stage of congestion and 
distension with the accompanying pressure and headache. 
It will be seen, then, that "depression of spirits" is usually 
a precursor of the headache, while both precede the 
explosion of urates from the circulation, either (i) out of 
the body entirely, by way of the urine, which is the normal 



URICACID^MIC MANIFESTATIONS. 99 

way, or, (2) out into the tissues (when elimination is im- 
perfect), which is the "rheumatic" way. 

Insomnia. — It is a well-known physiological fact that 
the amount of energy expended in the organism may be 
considered a fair index of the amount of cell destruction 
initiated and the consequent purin waste produced. 
Mental energy, in particular, necessitates cellular com- 
bustion. Both the mental and physical energy expended 
during the waking hours are chiefly of the voluntary 
character, and represent catabolic changes, — change from 
living to non-living matter. On the other hand, the little 
energy expended during the sleeping hours is entirely of the 
involuntary character, representing (1) anabolic changes, 
— change from non-living to living matter, as in cell re- 
establishment; and (2) continuation of catabolic changes, 
— removal of the non-living matter by the capillaries, into 
the general circulation, to be excreted by the kidneys. 
These latter two processes are a vegetative function, per- 
formed without any effort of volition, thus permitting of 
Nature's sweet restorer, "sleep," so long as voluntary 
action is not required. 

But, if an excessive amount of waste be present, from 
whatever cause, and blocks the cerebral capillaries, so 
that the distension causes even the slightest pressure on 
the surrounding brain tissue (especially the voluntary 
centers), the same effect is produced in making the subject 
restless, as from the pressure of a fly tickling the nerves of 
the skin, or of noises impinging on the drum of the ear, or 
strong light on the eyelids, etc. Any stimulus, which 
sends an impression to the centers of volition, excites an 
effort at voluntary action; but, as such action can only be 
performed when the subject is awake, the tendency is to 
arouse him from his sleep. 



100 URIC ACID AND ITS CONGENERS. 

In this indirect way, uratic excess, causing capillary 
obstruction and pressure, often results in insomnia, — 
especially if the pressure happens to be in the cerebellar 
region, in which the voluntary centers are chiefly situated. 

Headache Powders. — It has become well known to 
the laity that certain powders will relieve a headache; and, 
as a consequence, the indiscriminate sale of such powders 
has become enormous. They are usually composed of some 
antipyretic alkaloid in mechanical combination with caf- 
fein. The temporary relief afforded may be best explained 
by citing the action of cafTein, which is typical of all the 
rest, to wit: 

The crude material, which serves as a commercial 
source of cafTein, is tea, or "tea sweepings." At the great 
warehouses of New York and London, sales are made of 
waste and damaged tea. It not infrequently happens that 
whole cargoes of tea are damaged by moisture, being 
mouldy and unfit for the market. Such goes to the manu- 
facturing chemist, who extracts the cafTein. An infusion 
is made by extracting the tea with boiling water, and from 
this infusion the most of the organic matter is precipitated 
by a simple process. 

This vegetable xanthin (trimethyl-xanthin), like other 
alkaloids, and like the animal purins (as uric acid, itself), 
when first administered, lowers the alkaline reaction of the 
blood and clears out the urates by precipitating them into 
the tissues (often resulting in "rheumatic" symptoms), 
thus causing freedom of the capillaries and consequent 
diuresis. It operates, in this way, as a temporary stimu- 
lant, much like alcohol or opium, causing mental exhilara- 
tion and a feeling of well-being, — an effect which is due to 
the free flow of blood through the capillaries. 



URICACID^EMIC MANIFESTATIONS. 101 

Later, however, when alkalescence is restored, as it 
must be when all of the drug is absorbed, an excess of 
uric acid proportional to the amount of cafFein introduced, 
passes again into the blood; and, unless by some means 
it is speedily eliminated from the body, we get a return of 
the characteristic manifestations of uricacidaemia, — i. e., 
obstructed capillaries, scanty urine, defective secretions, 
loss of appetite, headache, etc. 

When cafFein is taken into the system, one-third of it 
appears in the urine as a purin body. Like xanthin, 
hypoxanthin, guanin, etc., cafFein is physiologically and 
pathologically identical with uric acid. For all intents 
and purposes its administration is equivalent to the ad- 
ministration of uric acid, and produces precisely the same 
physiological effects. Taken in the form of coffee, tea, 
headache powders, etc., it has become one of the great 
introducers of uric acid into the system. 

It is true, therefore, that headache is temporarily re- 
lieved by introducing more uric acid into the system, or 
substances from which it is derived, meat juice, beefsteak, 
sweetbread, coffee, etc. The efFect is similar to that 
experienced by the opium habitue, when taking another 
dose of the toxin which was responsible for the disagree- 
able symptoms which it now temporarily relieves. The 
action of sulfonal in relieving insomnia, is only temporary 
in efFect, and for a similar reason. 

The true remedial agent in these cases, is the one 
which tends to cure, by eliminating the offending substance 
from the system entirely, — not driving it temporarily into 
the tissues, where it either accumulates to cause "rheu- 
matic" signs, or is reabsorbed and gives rise to an aggra- 
vation of the original trouble and a demand for more of 



102 URIC ACID AND ITS CONGENERS. 

the same remedy, and so on, until serious consequences 
develop. 

The Neuroses. — As the elimination of a calculus 
is coincident with the disappearance of the pain which 
preceded it, we conclude that the calculus was the cause 
of the symptoms. Girls, during menstruation, often 
experience relief from pain on the elimination of a blood 
clot: a woman certainly does, after confinement, when 
the foetus is delivered. In both cases, the material elimi- 
nated was the cause of the symptoms complained of. 
We see the same thing in hepatic colic, on passage of the 
concretion and often in intestinal colic, on passage of the 
fecal mass. 

Reasoning by analogy, we conclude that the excess of 
urates, excreted immediately after the height of a neurotic 
attack, must have been the cause of the symptoms, — 
more especially as there was retention of the same, pre- 
ceding and at the beginning of the attack. In short, 
relief ensues upon their elimination. This finding is 
observed after various paroxysmal neuroses, such as 
hysteria, epilepsy, spasmodic asthma, chorea, "convul- 
sions " and " day terrors " of children, etc., and to a similar 
extent after the milder neuroses, as headache, that "tired 
feeling," the blues, etc. There would seem to be but one 
inference. 

Periodicity of Symptoms.— While uricacidaemic 
manifestations are not necessarily "explosive" or paroxys- 
mal to the degree noted in many of the neuroses, nev- 
ertheless there is always some periodicity to be observed. 
This is doubtless due to the natural periodic fluctua- 
tions in the reaction of the blood caused by the ingestion 
of three meals at regular hours each day, and to the cus- 



URICACID^MIC MANIFESTATIONS. 103 

torn of sleeping at a certain period every twenty-four 
hours. The periodic changes in the blood's alkalescence 
thus caused, lead to corresponding changes in the capil- 
lary flow, when urates are present in excess, which nec- 
essarily give rise to symptoms more or less periodic in 
character. 

There is a wave in all of Nature's phenomena, — 
physiologic as well as pathologic. In short, though excess 
of urates in a given case may be present at all times, 
the manifestations of such excess are likely to be only 
periodical, — as observed in the intermittent feelings 
of mental and physical "torpor," capricious appetite, 
lapses of memory, fits of depression, etc. The periodical 
changes in the amount of urinary water excreted and its 
contained urates, will be coincident with these subjective 
signs of "collaemia" or uricacidaemia. 



CHAPTER XII. 

(2) RHEUMATIC MANIFESTATIONS. 

The Beginning. — Just where the uricacidaemic 
stage leaves off and the rheumatic stage begins is not 
always easy to determine; yet it is, perhaps, most con- 
venient to consider that the rheumatic stage is ushered in 
when the urates of the obstructed capillaries in any given 
locality are no longer capable of being held in solution or 
suspension in the blood stream, but, owing to some excit- 
ing factor, (as exposure to cold, muscle-strain, etc.) are 
suddenly thrown down as a deposit on the adjacent tissue 
structures, where they may temporarily remain until 
restoral of the blood's alkalescence at that point causes 
their reabsorption into the circulation, to be conveyed en 
route to the kidneys for excretion, unless again thrown 
down as a deposit in some other locality. 

Muscular Stiffness. — Some idea of the manner in 
which " rheumatic" pains and aches are commonly caused 
by deposition of urates, and their infiltration between 
muscle fibres, may be gained from a physiological study 
of the stiffness or lameness which results from prolonged 
or violent muscular work of an unusual character. For 
instance, it sometimes happens, (as in the case of a pro- 
fessional man playing a game of base-ball), that the in- 
creased metabolism and augmented disintegration of 
nuclear muscle-cells and consequent purin cleavage, give 
rise to the formation of more waste of the uric acid type 
than can at once be taken up and removed by the lymph 
channels and capillaries in that locality, unaccustomed 



RHEUMATIC MANIFESTATIONS. 105 

as they are to such stress. Under these circumstances 
the excess of uric acid remains as a foreign body to clog 
muscular action, and we observe the stiffness which usually 
follows. The length of time during which such " stiff- 
ness" may remain, will depend chiefly on the activity of 
the eliminative organs in a given case, and the consequent 
cleaning out of the capillaries. 

Again, the increased nuclear destruction and greater 
metabolism may give rise to more purin cleavage and 
hypoxanthin than the xanthin-oxidase is capable of de- 
composing into uric acid, in which case the presence of 
xanthin or hypoxanthin in excess may serve to produce 
(perhaps through liberation of ammonia) some toxic or 
chemical change in the way of inflammatory action, — as 
observed in the heat and swelling of the overstrained 
tissues. We know, too, that the leucocytes will soon be 
increased in amount at such points, and it is possible that 
their disintegration produces purin cleavage in excess of 
the normal strength of the oxidase to form into uric acid. 
At this stage, even though the latter be formed satisfactor- 
ily, its considerable amount would probably be greater 
than could be taken up by the capillaries, and a temporary 
local deposit would result. 

The destruction of the nucleins, and the consequent 
change from guanin to xanthin, and adenin to hypoxan- 
thin, is best shown by the following schema, in which it 
will be observed that ammonia is liberated in both in- 
stances; to wit: 

C 5 H 5 N 5 0+H 2 0=C 5 H4N 4 2 +NH 3 

Guanin Xanthin Ammonia 



3 



C 5 H5N5+H 2 0=C 5 H4N 4 0+NH : 
Adenin Hypo Ammo- 

xanthin nia 



106 URIC ACID AND ITS CONGENERS. 

The further conversion of xanthin into uric acid is 
purely a process of oxidation brought about by a typical 
intracellular oxidase, the reaction being shown to its full 
extent by use of their respective constitutional formulae; 
to wit: 

HN — CO HN — CO 

II II 

CO C — NH\ CO C — NH\ 

| | CH+O --= | || CO 

HN — C— N/ HN — C — NH/ 

Xanthin Uric Acid 

These several changes of cell disintegration, from the 
splitting off of the purin bases to the oxidation of uric acid, 
take place seriatim', and, under normal conditions, the 
quantity formed is no more than can be taken care of by 
the venules and thus satisfactorily removed. But under 
the extraordinary conditions we are considering (pro- 
longed and violent muscular work), the removal does not 
keep pace with the increased supply, and blocking up of 
the capillaries in that vicinity results. Especially will this 
be true if the circulation at that point already contains an 
excess of uratic waste, as is often the case with a pro- 
fessional man. 

Uric Acid Explosion. — By an "explosion" of uric 
acid is meant that phenomenon of Nature, so often ob- 
served, when she is attempting to rid the circulation of an 
excess of urates. On such occasions, if the eliminative 
organs are active and equal to the emergency suddenly 
put upon them, the obnoxious urates will be expelled by 
way of the urine and feces; and the only subjective mani- 
festations of the explosion will be the depression of spirits, 
headache, etc., preceding the increased excretion. 



RHEUMATIC MANIFESTATIONS. 107 

But, on the other hand, if the patient be constipated, 
or the secretions otherwise locked up, the urates will be 
"exploded" out of the circulation into the tissues, and a 
"rheumatic" attack ensues, either of skin, mucosa, 
muscles, glandular organs, or in the joints themselves. 
Such "explosions" only occur, of course, after a prior 
retention of uric acid and consequent blocking up of the 
capillaries. In short, it is one of Nature's sudden changes 
from the uricacidaemic to the rheumatic stage of "Purin 
Excess." 

The objective signs, preceding an "explosion," and 
at the beginning of the headache, will be a scant, high- 
colored, over-acid urine, with high specific gravity, often- 
times extremely foetid. On some occasions, scalding 
during micturition will be observed. The liability to 
precipitation of calculi in the bladder is increased at such 
times, owing to the increased per cent, of urates in a given 
sample of urine; though the total quantity excreted 
during the twenty-four hours will be diminished. 

When the "explosion" occurs, (i. e., after the height 
of the headache attack), the quantity of urinary water is 
augmented and contains urates in excess of the normal; 
i. e., the daily excretion will be in excess. Urinalysis, 
before and during the decadence of the attack, will in- 
dicate first retention and then increased elimination, both 
of water and of urates. A sample of the scant, high-colored 
urine contains more urates than the same quantity of 
urine immediately after the headache; but less is elimina- 
ted during the twenty-four hours, at first. 

It should be understood, however, that the above 
holds good only when the eliminative organs are active and 
equal to the emergency at the time of the "explosion." 



108 URIC ACID AND ITS CONGENERS. 

In many cases, the retention and accumulation have so 
often been repeated, that the time comes when the excre- 
tory organs fail to meet the emergency, and the urates, 
being withheld, are driven into the tissues, and we get a 
"rheumatic attack." On such occasions, after the period of 
the headache, though the urinary water is increased in 
amount, as before, the excess of urates does not appear, — 
they have been driven elsewhere. In both cases, the 
diuresis is due to the freeing of the capillaries, when the 
urates are removed from the circulation. 

In the first instance, Nature has succeeded (by means 
of the " explosion") in ridding the system entirely of the 
excess; in the second, she has succeeded in relieving the 
circulation at the expense of the tissues, and " rheu- 
matics" supervene. The latter is usually the outcome 
whenever exposure to cold or muscular strain occurs just 
prior to the "explosion," thus lowering the alkalinity of the 
blood and tending to hasten precipitation of the urates be- 
fore they can be eliminated. 

Sites of the Deposits. — The muscles are oftener 
the seat of the deposits and infiltrations than other tissues, 
though the skin and mucous membranes receive their 
quota. Tissues subject to exposure and strain seem to be 
those for which the urates have the greatest predilection, 
doubtless because of the frequent lowering of alkalinity at 
these points, caused by such exposure and strain. The 
fibrous tissues of such joints as are most commonly sub- 
jected to strain, are also frequently affected. 

The efforts of the skin to serve as a vicarious avenue of 
elimination probably tends in some measure to stimulate 
the circulation of the surface vessels, at the time of an 
attempted "explosion," especially if the main excretory 



RHEUMATIC MANIFESTATIONS. 109 

organs are themselves inadequate; but, the great exposure 
of the bodily surface to influences of cold, tends to cause 
fluctuations in the alkalescence of the blood at that point 
and the consequent deposition of the urates, which pre- 
vents free elimination through the pores, resulting in 
checked excretion and such affections as a dry, scaly skin, 
eczema, psoriasis, etc. In fact, it is now the generally 
accepted opinion among dermatologists that many affec- 
tions of the skin which they are called upon to treat, are 
simply the manifestations of imperfect excretory function 
due to the presence of uratic deposits, and that local treat- 
ment alone will prove insufficient to effect a cure. 

Similar effects are observed in the mucous membrane, 
lining the respiratory tract, exposed to sudden and frequent 
changes of temperature through inspired draughts of air, 
as in the nasal passages, pharynx and bronchi, where such 
affections as coryza, nasal catarrh, hay fever, tonsillitis, 
bronchitis and spasmodic asthma are most common. 

In some cases of uric acid "explosion," in which the 
kidneys and bowels have proven unequal to the emergency, 
we witness the effects of retention of urates in this wise: 
1st., by their deposition from the surface vessels and the 
consequent irritation of skin or mucosa (as in eczema or 
tonsillitis); 2nd., by their deposition from the deeper ves- 
sels into the fibrous tissues of muscles or joints (as in 
muscular or articular rheumatism). The skin eruption or 
tonsillitis usually precedes the so-called "rheumatism" in 
these cases, although, strictly speaking, both are alike 
manifestations of the "rheumatic" stage of purin excess. 
One is not the cause of the other; both are due to a com- 
mon cause. They may alternate with each other or occur 
together in the same case. The same phenomenon is often 



110 URIC ACID AND ITS CONGENERS. 

observed in asthma or hay fever and rheumatism; but the 
latter trouble is simply a later manifestation of a "stage" 
common to both. 

Recent advocates of the bacterial origin of rheumatism 
offer in support of the germ theory the argument that ton- 
sillitis, preceding rheumatism doubtless means that the 
tonsils are a port of entry by which the germs gain access 
into the organism. But it would be just as rational to 
suggest that the skin is a port of entry, as observed in the 
eruption which often precedes the rheumatic attack. 
From the viewpoint we have taken, however, instead of 
their being "ports of entry/' to admit some external in- 
fectious agent, the mucosa and skin, in both instances, are 
attempting to serve as "ports of departure" for the exit of 
an internal autoinfectious agent. 

The twinges and lancinating pains, commonly des- 
cribed as "neuralgic," would seem to be caused when the 
deposit occurs in the sheathe of the affected nerve, at some 
point in its course, as observed in sciatica. 

Leg Cramps. — The cramps of the lower extremities 
are probably due to deposits in the muscles themselves, 
especiallv in the gastrocnemii and solei of the leg and 
plantar region of the foot. This region is particularly 
liable to deposits owing to the sluggish vascular flow here, 
explained on purely mechanical principles. Cold feet are 
similarly caused, as well as the varicose veins and chronic 
ulcerations common to this localitv. 

In the opinion of Macdonald (Cf. Northwestern Lan- 
cet, August 15, 1900): "The circulation in the leg has not 
only to overcome the force of gravity, but that of mechani- 
cal pressure from above as well; man, in fact, being the 
only animal in which the weight of the whole column of 



RHEUMATIC MANIFESTATIONS. Ill 

blood contained in the vena cava presses directly upon the 
veins of the lower limbs. Unlike other veins, the cava is 
not supplied with valves; and it will at once be seen, in 
recalling the action of the hydraulic press, what a powerful 
effect the weight of its column of blood must have. This 
defect in the structure of our vascular system, — i. e., the 
cessation of valves at just the point where they would be of 
the most use in the erect posture, — is only another of the 
manv significant proofs in favor of the evolutionary theory 
of growth and development. The indication is that man 
has assumed his present upright position within so com- 
paratively recent a period that the body is not yet perfectly 
adapted for it; for, in other animals, of course, the cava 
lies in a horizontal position in which valves are not es- 
sential. " 

"It will be observed that persons subject to cramps 
are worse at night, after a day in which the body has been 
forced to assume the erect position, as in standing con- 
stantly at work at a bench. The mechanical effect upon 
the veins of the lower limbs, preventing the return venous 
flow, may be seen, too, in the results which follow after 
having been seated for some time in the well-known " cross- 
legged" position, — when severe cramps in the leg so 
crossed (usually the left) will often be the consequence. 

"The same effect is often observed in chronic consti- 
pation. The colon, containing an accumulation of feces, 
presses on the iliac veins (more particularly on the left side 
when partial impaction of the sigmoid flexure occurs) 
causing congestion of the leg veins, producing cramps, 
cold feet, etc. This is especially the case in elderly people, 
who are usually constipated, and in whom the walls of the 
colon are partially atonied. It has been said that "washing 



112 URIC ACID AND ITS CONGENERS. 

out the colon," has often been resorted to as an effective cure 
for cold feet. Cramps and cold feet, too, are troublesome 
at times to the pregnant woman, owing, probably, to the 
pressure exerted on the iliac veins by the gravid uterus." 

"It will be seen, from what has been said, that an 
obstructed or sluggish circulation in the lower limbs, result- 
ing in defective nutrition of the muscles of that locality, is 
a constant predisposing cause of cramps, and that in any 
rational treatment of the same, this fact should be borne in 
mind. The products of metabolism and tissue waste, 
which should be immediately removed from the body, are 
allowed, owing to obstruction to venous return, to remain 
behind to vitiate the surrounding structures. Especially 
is this the case in persons of the gouty diathesis, who are 
notoriously subject to cramps. Uric acid, a product of 
purin metabolism, is, in these people, deposited in the form 
of urate salts in the muscles surrounding the congested 
veins of the leg and foot, interfering with nutrition and 
serving mechanically as an irritant and direct cause of 
spasmodic contractions." 



CHAPTER XIII. 

(3) GOUTY MANIFESTATIONS. 

Characteristics. — It is a common error to consider 
that gout is restricted to the foot or toe. While it is true 
that the phalangeal joint of the big toe is one of the most 
favorable localities for the formation of uratic concretions, 
it is by no means the only one. In whatever part of the 
body the physical and chemical environment is such that 
the precipitation and crystallization of urates may take 
place, gouty manifestations in that locality may result; 
but such environing conditions are very rarely met with 
except in two or three distal positions, unless under very 
unusual circumstances. 

Gout is characterized by the formation of crystalline 
urates or concretions, whose presence generally gives rise 
to disturbances accompanied with great pain. The gouty 
patient is not so much of an invalid, except from the pain 
he suffers and t-he enforced quiet he must observe, no 
matter whether the concretion be in the metatarsophalan- 
geal joint, in the renal tubules or pelvis, the ureters or the 
bladder. 

Genito-urinary Concretions. — One portion of the 
organism in which there is a strong tendency for the urates 
to precipitate themselves in crystalline form, is in the 
genito-urinary tract, — the renal tubules, pelvis, or the 
bladder. In each of these, localities, the crystallization is 
most likely to occur when the urine is scant and concen- 
trated, and some solid substance is present around which 
the crystals may group themselves. 



114 URIC ACID AND ITS CONGENERS. 

According to Prof. Byron Robinson, of Chicago, who 
has made a special study of the aetiology of uric acid cal- 
culus: "The maintaining of uric acid in suspension, non- 
precipitated, not in concretions, is supposed to be due to 
the colloidal properties of the urine aided by its coloring 
material, — pigments. For example, the darker colored che 
urine, the more uric acid it holds in suspension. The more 
concentrated the urine, the more liability to precipitation 
of uric acid. If there is a small, weak stream, uric acid 
calculus forms with facility, and is liable to lodge as a con- 
crement. The maximum concentrated solution of urine 
tends to crystallize with vastly more facility and frequency 
than dilute urine. Single crystals are rapidly floated 
through the ureter by diuresis, while in small quantities of 
urine with a weak stream, the crystals tend to lodge and 
increase in dimension." 

It will be seen that oliguria is the best condition for the 
multiplication of uric acid calculus. Cardiac disease, with 
resulting partial stasis and congestion is frequently the 
precursor of ureteral colic and haematuria, — i. e., calculus 
rapidly forms. 

Human urine contains usually about one part uric 
acid (commonly urate of sodium) to one thousand. When 
the sodium urate exceeds one to one thousand parts of 
urine, it is frequently deposited as a sediment in the ex- 
creted urine, either immediately, or shortly on standing. 
The deposit of uratic crystals, so often seen in urine in the 
form of sand, gravel, brick-dust or red pepper grains, can 
be regarded as pathologic only when the precipitation 
occurs within four to six hours subsequent to the evacuation 
of the urine. Excessive and rapid uric acid crystallization 
subsequent to urination indicates that the crystallization 



GOUTY MANIFESTATIONS. 115 

may occur previous to the voiding of the urine, endanger- 
ing the precipitation of uric acid and the formation of 
calculus. 

Concretions in Toe Joints. — The excruciating pain 
caused by the presence of a concretion in the genito- 
urinary tract has been supposed to be due to the pressure 
produced on adjacent sensitive tissues, which would like- 
wise result from the presence of any other solid foreign 
body of irregular contour. The pain in the toe joint is 
probably due to the same mechanical cause to a great 
extent; but, in this location, as the concretion cannot 
escape and steadily increases in size, inflammatory dis- 
turbances, with swelling of the tissues, add to the pressure 
and pain. 

It has already been explained, in a previous chapter, 
why the circulating blood itself, though it may contain an 
overplus of urates, is not an eligible site for the formation 
of concretions. To the several reasons therein given may 
be added the two, referred to by Prof. Robinson as being 
operative in the case of the urine: i. e., (i) its colloidal 
properties, and (2) the presence of a pigment, — both of 
which are more pronounced in the blood than in the urine. 
The feeble flow of the current, mentioned by him as a 
factor favorable to the precipitation of urates in the urine, 
is even better illustrated in the case of the toe joint, where 
the lymph stream is practically motionless at the time the 
shoe is worn. Then, too, the lymph and synovia lack the 
pigment and colloidal character of the blood, rendering 
either of the former a favorable medium for crystalliza- 
tion of the urates as soon as dialyzed from the capillaries, 
— as in the case of the tubules and pelvis of the kidney 
as soon as the urine is dialyzed from the blood. 



116 URIC ACID AND ITS CONGENERS. 

Other Tissues. — Urates are occasionally precipi- 
tated in crystalline form in parts poorly vascularized on the 
bodily surface, as at certain points in the skin, in the bursa 
of the elbow, and in the helix of the ear. In the latter 
situation, true concretions are found and sometimes in the 
skin, though usually laminae or scales are found here. The 
nasal septum is frequently a site, and rhinologists are now 
inclined to attribute many cases of hay fever and chronic 
nasal catarrh to this irritant factor; though, as a rule, 
patients with these disorders are still in the "rheumatic" 
stage. 

The microscopic deposits which occur in the coats of 
cerebral arteries, in men of advanced age, who have been 
subject to years of constant and severe mental strain, are 
sometimes of the minute crystalline form, and indirectly 
lead to the brittleness of the parts and final rupture at the 
moment of some sudden distension of the vessels, e. g., 
as observed in apoplexy. Occasionally, too, the deposits in 
the cardiac valves become crystalline, and similar sudden 
fatalities result, — as in so-called "heart failure." 

In all of these instances, the person affected is as much 
a "gouty subject" as he who has the classical concretions 
in the metatarsophalangeal joint of the great toe. The 
victim of atheromatous arteries, or of endocarditis (mitral 
stenosis) or of hay fever in its chronic form, or of kidney 
stones, or even of "gravel" in its later manifestations, 
may be said to have reached the "gouty stage" of purin 
excess; and he has generally passed through the same 
"uricacidaemic" and "rheumatic" experiences as the man 
with the typical gouty foot. 

Objective Signs. — As in the primary and secondary 
stages, the urine, prior to an acute attack or "explosion" 



GOUTY MANIFESTATIONS. 117 

in gout, is scant and concentrated. t ]iough less urates than 
normal are excreted during the twenty-four hours. From 
the moment of the height of the attack, during the sub- 
sidence of the pain and other symptoms, the urine begins 
to increase in amount, both as to water and urates, until 
the excretion becomes greatly in excess of the normal. 
In short, previous retention and subsequent elimination 
are as characteristic of the gouty explosion as of the 
rheumatic explosion. 

Experimental Production of Gout. — In the 
Berliner Klinische Wochenschrift, No. I, page 7, 1900, H. 
Kionka reports some interesting facts respecting the pro- 
duction of experimental gout in domestic fowls. The 
fowls were kept in cages and fed exclusively on hashed 
horse meat, which had been previously stripped of sinew 
and fat. As much water as they wished to drink was al- 
lowed. 

The fowls took to the new diet very rapidly, and at 
the start it seemed to agree with them very well. But, 
after some time, ordinarily in from three to five months, 
they began to show 'signs of disorders presenting all the 
characteristics of gout. 

The disease assumed different forms. In one variety, 
in which the symptoms appeared at an early date and ran 
a rapid course, the first change observed in the fowls was 
that their gait became uncertain, and that they fell to the 
ground after hopping ofT their perch. The weakness in 
their legs went on increasing, and, on certain days, when 
probably the pains were felt with more severity, they re- 
mained lying down, with their legs drawn under them, 
and took no food. Their joints were manifestly swollen. 
These attacks lasted a few days, after which the swelling 



118 URIC ACID AND ITS CONGENERS. 

of the joints disappeared? and the fowls again began to eat 
and walk about. 

After some time, the attacks became more and more 
frequent; appetite disappeared; the fowls became thin 
and died. In this form of the disease, slightly marked 
deposits of urates were found around the joints when 
examined post mortem. The tophi were well developed in 
a second variety of the disease, which was not attended 
with real attacks of gout, as in the first mentioned cases, 
but which presented only a simple, temporary aggrava- 
tion of the accidents of gout, i. e., an uncertain gait and 
pain in walking. In these cases, when examined post 
mortem, the tophi, which were well marked, were found in 
the joints and between the sheaths of the tendons of the 
legs and claws. The third variety of gout affected the 
viscera, with deposits of urates on the serous membranes, 
and infarcts of uric acid in the kidneys. In all these 
varieties of gout the kidneys of the fowls, when examined 
post mortem, were found to be affected with gouty neph- 
ritis. 

Another experimenter, whose researches have at- 
tracted wide attention, is Freudweiler. In order to decide 
the question whether the deposits of urates in the tophi 
form the primary lesion, or whether they are (according to 
Ebstein) secondarily deposited in the injured necrotic 
tissue, he made numerous injections of sodium biurate. 
He could demonstrate that the deposit used, acts injurious- 
ly on the tissue, leading to an extensive reactionary in- 
flammation. The inflammatory foci, thus produced ex- 
perimentally, differ histologically in no way from the tophi 
of gout. Based on these results, Freudweiler does not 
believe it probable that the uric acid deposition is preceded 



GOUTY MANIFESTATIONS. 119 

by a tissue necrosis; he agrees with the explanation first 
given by Garrod, that the tissue lesions are caused by the 
deposition of urates. 

In 1884, Gaucher discovered that the injection into 
the body of a healthy animal of small quantities of xanthin 
and hypoxanthin produced marked changes in the excre- 
ting cells of the kidney parenchyma {nephrite epithehale), 
similar to the lesions found in gout. Kolisch and Tandler 
observed the same. More recently, Croftan observed by 
similar investigations that granular atrophy of the kidneys 
was produced identical with this nephrite epithelialet 
which is a constant precursor of gout. 

In Croftan's "Experiment IX," a guinea pig received 
daily injections hypodermically of a 0.5 per cent, watery 
solution of xanthin for a period of seventy days. After 
four weeks, albumin was found in the urine. The animal 
was killed at the expiration of the seventieth day and the 
kidney parenchyma submitted to microscopic examina- 
tion. A granular degeneration of the epithelial cells lining 
the tubuli contorti and a proliferation of the endothelium 
of the intertubular capillaries were found. The picture 
corresponded in every way with the form of nephritis 
observed in the formative period of true gout. 

Intestinal Lithiasis. — Concretions are not only 
found in the tubules of the kidneys as above described, 
but in the intestinal canal. In the Revue de Therapeutique, 
Vol. LXVIII, 397, Vibert discusses the occurrence of this 
gouty manifestation under two forms: 1. Those forms 
of concretions which do not originate within the canal it- 
self, such as pancreatic or biliary calculi. 2. Those origina- 
ting in the canal, existing either in the form of intestinal 
sand or as well matured calculi. Colic is the most pressing 



120 URIC ACID AND ITS CONGENERS. 

symptom calling for relief here, as in the case of renal 
concretions and of phalangeal gout. 

Frequency of Gout. — Futcher considers the oc- 
currence of the disease throughout the country, and sum- 
marizes his views as follows: 

"(i). Gout in the United States is undoubtedly more 
common than is generally supposed. (2) Out of 13,400 
medical cases admitted to Dr. Osier's wards in the Johns 
Hopkins Hospital during a period of thirteen years, there 
were thirty-five gout cases, or 0.24 per cent, of the total 
number of patients. For the same number of years at 
St. Bartholomew's Hospital there were 116 gout cases out 
of a total of 31,100 medical admissions, or 0.37 per cent, 
of the cases. Thus, among hospital patients gout is only 
about one-third more frequent in London than in Balti- 
more. (3) All of the thirty-six cases were white males. 
The largest number of cases occurred in the fifth decade. 
Twenty-seven of the patients were native-born Americans. 
(4) The majority of cases appear to have earned rather 
than inherited their gout. Alcohol and lead seemed to be 
the most potent predisposing aetiological factors. (5) 
Thirty-three of the thirty-six cases had reached the chronic 
stage before they came under observation. In seventeen 
of the cases tophi were present. (6) Among the more 
interesting complications, may be mentioned three cases 
of gouty bursitis; one case of parotitis; one of pericardi- 
tis; one of retrocedent gout, with symptoms simulating 
intestinal obstruction. (7) There was evidence of disease 
of the kidneys in the majority of the cases. Albuminuria 
occurred in twenty-seven, and hyaline and granular casts 
in twenty-three instances. (8) Arteriosclerosis was present 
in twenty-three cases, and a mitral systolic murmur in 



GOUTY MANIFESTATIONS. 121 

five. (9) Many gout cases are mistaken for rheumatism. 
Four of the cases were repeatedly diagnosed as such on the 
early admissions, the appearance of tophi later revealing 
their true nature. (10) The series illustrates the great im- 
portance of examining the ears and the vicinity of the 
joints for the presence of tophi in all cases of multiple 
arthritis." 



CHAPTER XIV. 

SEQUELAE AND COMPLICATIONS. 

Constipation. — Mathews says: "First try and 
ascertain what is the cause of the constipation. In this con- 
nection, I wish to state that after an examination and 
observation of these cases extending over twenty years, I 
am forced to believe that the majority of them have as a 
basis a constitutional derangement. In trying to solve the 
problem, it was observed that many of these patients were 
of a rheumatic or gouty diathesis. Acting upon this hypoth- 
esis, I have treated them by combating this special 
trouble and have found that in many cases the constipation 
would take care of itself. My theory is that in the rheu- 
matic or gouty subject, the intestines are brought under the 
same conditions that the disease or diseases are made man- 
ifest in other portions of the body. The muscular coat of 
the intestine is particularly afTected by the gouty con- 
dition, and in consequence loses its contractile power." 

In any effort to explain the ^etiological relationship 
which is known to exist between certain cases of consti- 
pation and uric acid retention, the following three facts 
must be borne in mind, viz.: i. The alimentary tract is 
practically outside of the true interior of the body; its 
mucous membrane is, in reality, a continuation of the skin, 
and before any substance can enter the system proper, it 
must be absorbed or osmosed through this gastro-intestinal 
lining. 2. The intestinal lining is supplied with capillary 
vessels and their attendant nerves in a similar manner to 
the skin, and they are subject to the same chemico_ 



sequels: and complications. 123 

mechanical influences, — e. g. , heat and cold, alkalies 
and acids, pressure, etc. 3. When waste material from 
the food introduced has reached the "fecal reservoir" 
(especially the sigmoid and rectum) it is a foreign body, 
containing nothing than can benefit the system and much 
that is actually harmful and should therefore be removed 
from contact with its surroundings as soon as possible. 

If this "foreign body" is not removed, but remains to 
accumulate with others of a like character until the walls 
of the intestine are distended with pressure: What is the 
mechanical effect upon the capillaries ? Their flow is 
necessarily impeded. The returning veins below that 
point, especially the rectal veins, are congested, and 
hemorrhoids result. Moreover, if uric acid is present in 
excess in the circulation, it will eventually be deposited at 
this point and a nidus of urates be formed as in any other 
portion of the bodily surface where the circulation is im- 
peded by strain or pressure, as in the toe joint owing to 
pressure of the shoe. The fibrous coats of the colon and 
rectal walls being thus infiltrated with urates of soda, intes- 
tinal gout arises, muscular contractions are more or less 
impeded and loss of peristalsis follows; while the circu- 
lation being impeded at the same time, the parts are illy 
supplied with nutritive material, and atony results. 

That the "colic" and constipation following the 
steady introduction of lead and iron into the system are due 
to deposits in the fibrous tissues, producing a gouty con- 
dition of the bowels resembling that caused by the soda 
biurates, is a fact now becoming recognized by some of our 
most careful investigators. It has been shown that lead 
and iron (like zinc, mercury and other metals) form in- 
soluble compounds with uric acid, which are precipitated 



124 URIC ACID AND ITS CONGENERS. 

out of the blood into the connective tissues at those points 
where the conditions are especially favorable, as in the 
fibrous coating of the intestinal tract. It is well known that 
lead colic can be successfully treated by the same thera- 
peutic agency that has been found efficacious in typical 
gouty conditions, and that the colic, constipation, etc., are 
produced by the irritant effects of urate of lead in the 
intestinal walls in the same manner as above described in 
the case of the urate of soda. 

Moreover, that the same aetiological factors which are 
usually mentioned as being instrumental in the production 
of gout, or the "gouty" tendency, may also, eventually, 
cause constipation, will be readily understood when 
remembering that both are often due to the same chemico- 
mechanical influences; i. e., an obstructed circulation in 
the parts affected, and deposition or formation of uratic 
salts (of soda, of lead, of iron, of zinc, etc.) at that point. 
Of course the additional effect produced by a lack of 
biliary secretion in cases of hepatic insufficiency, leading 
up to the loss of peristalsis owing to distinctly chemical 
reasons, is a matter outside of the uric acid field in consti- 
pation, except in so far (and this is important) as an excess 
of uric acid may serve to obstruct the capillary flow in the 
liver cells and thus interfere with the quantity of bile 
secreted. The pancreatic and intestinal glandular se- 
cretions may also be rendered scant in amount for the same 
reason, (i. e., a general "collaemia") and the bowel con- 
tents become more difficult to expel owing to the lack of the 
proper semi-fluid consistence. 

Again, owing partly to the absorption into the general 
circulation of toxic material from the contents of the "fecal 
reservoir/' partly to the impeded capillary flow throughout 



SEQUELS AND COMPLICATIONS. 125 

the intestinal walls, giving rise to impaired nutrition, and 
partly to the lowered alkalescence of the blood (from 
intestinal absorption), causing sufficient change of solubil- 
ities for uric acid in that fluid as to result in the precipi- 
tation of the latter in colloid form into the capillaries 
throughout the body, thus obstructing their flow, — a train 
of evils results such as usually accompanies or follows con- 
stipation: headache, dizziness, lassitude, mental hebetude, 
irritability, loss of appetite, etc., including yarious other 
functional disturbances brought on as the direct or indirect 
result of this abnormal condition. In other words, 
"collaemia" will be produced in all cases wherever an 
excess of uric acid exists at the time of the constipation; 
and if the latter should be permitted to become chronic, 
the uric acid excess will subsequently become increased as 
the result of a lowered general metabolism. In this way, a 
"circulus vitiosus"is established. 

Hepatic Insufficiency. — As one writer graphically 
says: "The liver has sometimes been called the 'human 
grate.' It is all of this; for it not only stands guard over 
the burnt up material of the system, sifting out the cinders 
and ashes of combustion from the general circulation, but 
also serves as a barrier against the entrance of undesirable 
or overplus fuel from the bowel by way of the portal circu- 
lation. This intimate relation existing between the liver 
and the bowel is a sufficient reason why hepatic disorders 
usually follow or accompany digestive or intestinal dis- 
turbances. A blockade in the rectum means a disturbance 
of the portal circulation and the loading of a heavy burden 
upon the liver. As the most important centre of the ab- 
dominal venous system, the blood supply to this organ is 
enormous; and it will at once be seen that if the bowel exit 



126 URIC ACID AND ITS CONGENERS. 

be choked with waste, much will be absorbed and carried 
to the human grate which must itself become 'clogged' 
in the endeavor to unload the burden." 

Whenever the liver fails to remove the burnt up tissue 
waste, the circulation becomes charged with ashes and 
clinkers. In short, the "grate" of the system has become 
clogged and the fire is being deadened with the products of 
its own combustion. The blood abounds with deleterious 
matters choking up the smaller vessels, which interferes 
with the nutrition of every important organ and tissue of the 
body. Bilious congestion and stasis exist, which may 
result in an increase of connective tissue growth and 
partial fatty degeneration of cells. Hyperemia of other 
glandular organs ensues, their secretory and excretory 
functions are both imperfectly performed and the system 
necessarily becomes loaded with toxic waste — of which 
catabolic products of the uric acid type are the most com- 
mon. The typical symptoms of hepatic insufficiency, due 
to obstruction of its capillaries with an excess of urates, are 
such that we know something is wrong with the liver; to 
wit: "bad taste" in the mouth, heavily yellow-coated 
tongue, nausea, thirst, anorexia, epigastric fullness, flatu- 
lency, headache, vertigo, constipation, yellowish con- 
junctiva, languor, debility, countenance sallow and worn, 
urine scanty and high colored, containing "brick dust" 
deposits and bile pigments. 

Acid Dyspepsia. — The failure of the liver to perform 
its normal oxidizing function, owing to capillary obstruc- 
tion from urates, often results in a scanty secretion of bile 
into the duodenum and consequent decomposition of food 
from lack of this essential antiseptic. As is well known, 
food decomposition is one of the most conspicuous evi- 



sequels: and complications. 127 

dences of intestinal indigestion, resulting in sour eructa- 
tions and the so-called "acid dyspepsia." If an examina- 
tion of the urine at such times, points toward uricacid- 
aemia, that method of treatment will prove most effective 
which aims at the elimination of urates from the system, — 
much more effective than if attention is directed simply 
toward the local gastro-intestinal symptoms. In other 
words, a uric acid solvent and eliminant will give more 
satisfactory results than a purely digestive agent, such as 
pepsin, pancreatin, etc. 

Renal Inadequacy. — The intimate relation of 
cause and effect, as observed between kidney disease and 
uric acid retention and accumulation, or vice versa, has 
long been recognized; and such expressions as "gouty 
kidney," "lithaemic nephritis," etc., are commonly found 
in most of our text-books on medical practice. Garrod's 
theory that, in gout, the alkalinity of the blood is lessened 
and the amount of uric acid in circulation increased 
owing to deficient power of elimination on the part of the 
kidneys, is now quite generally accepted as true. 

According to Futcher: 'The most probable ex- 
planation for the increase is that it is due to a diminished 
excretion of uric acid by the kidneys with consequent 
retention in the circulating blood. Minkowski, who has 
comparatively recently reviewed the evidence, supports 
this theory. Hans, Vogt and Reach have shown that the 
output of uric acid after the ingestion of nuclein-containing 
food is much less marked in the gouty than in the healthy 
individual. Garrod was of the opinion that the excess of 
uric acid in the blood was due to the nephritis present. 
It is a well-known fact that in chronic gout, serious organic 
disease of the kidneys occurs. It has been suggested that 



128 URIC ACID AND ITS CONGENERS. 

even before any organic disease of these organs develops, 
there may be a 'functional' disturbance of the secretory 
elements. " 

Minkowski and His, Jr. have advanced the view that 
the uric acid in gouty individuals circulates in the blood in 
a different organic combination than in the blood of 
healthy persons, and that consequently the kidneys are 
functionally incapable of eliminating the acid in the same 
way they do in normal metabolism. Whatever the true 
explanation of the phenomenon may be, the fact is recog- 
nized that a diminished excretion of uric acid by the 
kidneys occurs in gout. The recent investigations of Mac- 
alester corroborate this. 

When we consider the constancy and rapidity of 
tissue change, the large mass of new material to undergo 
construction, and of waste material to be disposed of 
and that the kidney is at once the avenue for the removal 
of the most complex forms of tissue waste, and the by-path 
along which the absorbed products of intestinal decom- 
position are removed; that it is also subject to marked and 
frequent variances in the quantity of the excretory mater- 
ials delivered to it,— then it is not surprising that the 
selective function of the renal filter should occasionally 
become disordered, and elimination by that channel be 
imperfectly performed. 

Furthermore, in such an atmospheric medium as we 
live, where sudden exposures to chills occur, the function of 
the skin is depressed and an undue share of the work of 
elimination is again thrown upon the kidneys. But it is 
not altogether, in this case, simply an excess of work that 
the kidneys are called upon to do, for, as is well known, 
suppression of the perspiration is followed by increased 



SEQUELAE AND COMPLICATIONS. 129 

acidity of the urine, and from this we may infer diminished 
alkalinity of the blood, leading to the accumulation of uric 
acid in the circulation, and the deposition of its salts in 
the various tissues of the body, including the canaliculi of 
the kidney itself. 

In summing up, therefore, it may be said that pre- 
ceding the stage usually denominated "Bright's disease," 
an auto-intoxication process has been going on, resulting 
in a vitiated circulation and the diseased condition known 
as "uricacidaemia," among the more direct causes of which 
may be enumerated the following, to wit: I. Excessive 
nitrogenous or purin waste from "high living" (or from 
certain fevers). 2. Increase of the raw material from 
which uric acid is formed, i. e., the excessive use of nitrog- 
enous foods, or foods rich in nucleins. 3. Gastrointes- 
tinal indigestion and fermentation, from overfeeding, etc., 
4. Absorption of the products of retained fecal matter in 
constipation. 5. Any factor causing functional disturb- 
ance of the liver, — the great urea-forming organ of the 
body, — resulting in the presence of an excess of uric acid 
unoxidized. 6. Frequent chilling of the bodily surface, 
which checks perspiration from the skin, resulting in sub- 
alkalinity of the blood, the retention in excess of uric acid 
in the circulation and subsequent deposition in the various 
connective tissues of the body. 

Urea Retention. — In the more advanced stage of 
the disease process, after constant irritation of the tubules 
has resulted in anatomical or histological changes in the 
kidney and impairment of its excretory function, it has: 
been seen that certain of the urinary constituents are re- 
tained in the circulation, the most important of which is 
urea, a waste product constantly produced in the metabo- 



130 URIC ACID AND ITS CONGENERS. 

lism of every organism wherever there are changes in 
proteid matter. The daily average production of urea, in 
man, has very little variation, the human organism elim- 
inating about one ounce in twenty-four hours. Its re- 
tention gives rise to a violent toxicosis, having many of the 
clinical aspects of poisoning from strychnia. The human 
economy generates enough in eight hours to render life 
extinct. It is, therefore, upon the elimination of this 
waste that life may depend; and the non-elimination of 
it presents many clinical conditions, from a dizzy head- 
ache to uraemic coma and fatal eclampsia. From this it 
will be seen that defective elimination of proteid waste, 
i. e., urea, rather than abnormal loss of the proteid itself, 
i. e., albumin, is what demands our chief attention in 
Bright's disease. 



CHAPTER XV. 

URINARY ANALYSIS. 

Ocular Inspection. — The general practitioner may 
gain much valuable knowledge of his patient's faulty 
metabolic condition, from a mere physical examination of 
the urine from time to time. If he suspect uric acid ac- 
cumulation from the general symptoms, he may feel more 
certain of his diagnosis if certain urinary signs are present. 
Inasmuch as Nature constantly strives to rid the organism 
of an excess of such waste, there will doubtless be times 
when she succeeds in the effort, and the urine will give 
evidence of the fact. 

If the urates are about to be excreted in excess of the 
normal (or an attempt at such excessive excretion is being 
made), ocular inspection at that time will show a high- 
colored urine, in which brick dust deposits are thrown 
down in greater or less, amount within three or four hours 
after voidance, attaching themselves in a few hours to the 
bottom and sides of the container, often requiring the 
application of hot water and sapolio and a vigorous scrub- 
bing to effect their removal. 

The twenty-four hours' quantity of urine in these 
cases may be less than normal, specific gravity high and 
the reaction overacid. Even, therefore, though the pre- 
cipitation apparently be due to excessive acidity and a 
lessened amount of water, it is safe to infer that Nature is 
struggling to eliminate uratic waste from the system, not- 
withstanding that the reduced alkalinity of the blood (as 
thus indicated) tends to further its retention and accumu- 



132 URIC ACID AND ITS CONGENERS. 

lation. In either case, it is pointed out to the physician 
that eliminative aid should be furnished. 

Such attempted uratic explosions will be observed either 
in acute cases, or at the time of exacerbations in chronic 
cases, — during the attack at its height and as it is passing 
off. Had the urine been inspected during the few days 
preceding the attack in acute cases, or during the inter- 
vals between attacks in chronic cases, it would have been 
found more copious and less highly colored, with little 
or no signs of precipitation. It is, in fact, at these times 
that the excreted urates are subnormal in amount, and re- 
tention occurs. 

If ocular inspection has shown a scant, high-colored 
urine, with tendency to precipitation of urates, as above 
described, the physician should remember that the same 
tendency to precipitation at such times also holds true in 
the bladder and kidneys, where calculi will be formed. As 
already quoted from Prof. Byron Robinson : " If there is a 
small, weak stream, uric acid calculus forms with facility 
and is liable to lodge as a concrement. The concentrated 
urine tends to crystallize with vastly more facility and 
frequency than dilute urine. Single crystals are rapidly 
floated through the ureter by diuresis, while in small 
quantities of urine with a weak stream, the crystals tend 
to lodge and increase in dimension." (Cf. American 
Medicine, Aug. 26, 1905, p. 366.) 

It will thus be seen that a mere physical examination 
of the urine often furnishes the physician with sufficient 
evidence to warrant him in adopting the akaline elimina- 
tive treatment to effectually combat the two-fold danger 
which threatens his patient; viz: 1. The tendency to 
retention and accumulation of urates (as shown by at- 



URINARY ANALYSIS. 133 

tempted "explosions")- 2. The tendency to irritation of 
the kidnevs and bladder, and the formation of calculi. 

Alkaline Urine. — The irritation of the mucous lin- 
ing of the bladder, caused by the presence of urate crystals 
in abundance, in a strongly acid urine of the character 
above described, leads oftentimes to a certain well-known 
urinary phenomenon of positive diagnostic significance. 
It will be observed, for example, if the excreted urine 
remains scant and over-acid for some time, that, eventually 
symptoms referable to the bladder will be complained 
of, and the urine becomes ammoniacal in odor and alka- 
line in reaction. How is this to be accounted for ? 

The explanation is simple enough. The urine which 
passes through the ureters into the bladder, being hyper- 
acid and loaded with urate crystals, causes, by means of 
this two-fold irritation, a congestion or catarrhal inflamma- 
tion of the bladder surface, which results in the production 
of mucus, pus, or other inflammatory products. The 
latter, when admixed with the bladder urine, produces 
ammoniacal decomposition or alkaline fermentation, — 
the same as is observed in all urines when exposed to the 
air, a few hours after voidance. As a result, in the cases 
we are considering, therefore, the urine is alkaline when 
voided; notwithstanding that at the moment of its entering 
the bladder from the ureters it was strongly acid. 

From this it will be seen that if the urine is alkaline 
when first voided, cystitic trouble is probably existent. 
If this alkalinity be found to be due to a volatile alkali 
(ammonium), then we may be sure that ammoniacal 
decomposition has taken place in the bladder owing to the 
presence of catarrhal or purulent inflammatory products. 

It should be understood, of course, that alkaline urine 
is sometimes caused by the presence of the fixed alkalies 



134 URIC ACID AND ITS CONGENERS. 

(sodium, potassium, lithium), such as occurs when the 
alkaline remedies are being taken. To determine beyond 
doubt whether the alkalinity be due to a volatile or to a 
fixed alkali, the following simple plan is recommended; 
to wit: The litmus which has been turned to blue is ex- 
posed to the air until it has become thoroughly dry. If 
the blue color remains, it was due to a fixed alkali; if not, 
to a volatile alkali. In the latter eventuality, we know 
that the bladder is more or less inflamed; we immediately 
suspect uric acid irritation and employ the alkaline elimin- 
ative treatment. 

It seems unnecessary, after what has been said, to 
point out that the mineral acids are contraindicated in the 
class of cases under discussion. 

Retention of Solids. — It is well known that the 
daily expenditure of energy and "wear and tear" of the 
animal cells result in the corresponding excretion of a 
certain amount of waste solids in the urine; that, as a rule, 
about seven and one-half grains of these solids are excreted 
for every pound of body weight, so that a man in the prime 
of life, weighing 160 pounds, normally excretes 1200 
grains of urinary solids every twenty-four hours. Of this 
amount, one-half is composed of urea. 

It often happens, in the later stages of Bright's 
disease and in serious hepatic disorders, that urea is not 
being properly eliminated; while uric acid has been only 
partially eliminated for some time previous, giving rise to 
various symptoms indicative of retention and accumula- 
tion. Though, of course, quantitative estimations are 
essential to an understanding of the exact amount of these 
waste products which is being eliminated; nevertheless, 
for ordinary practical purposes, the approximate total 



URINARY ANALYSIS. 135 

amount of solids excreted may first be ascertained, from 
which it is readily determined whether urea and the urates 
are being retained to any great extent — even judging very 
fairly of the total amount of the former waste product. 
At all events, if retention of solids be discovered, especially 
when symptoms of toxaemia coexist, no further evidence is 
required to demonstrate the need of employing the alka- 
line eliminative treatment as an effective aid to the meta- 
bolic and excretory organs during this emergency. 

In determining the approximate amount of solids 
excreted in the urine daily, the "Haines-Bulkley Rule" is 
doubtless the method most extensively utilized in actual 
practice today; to wit: 

"Multiply the last two figures of the specific gravity 
by the total number of ounces of the twenty-four hours' 
urine, and add to this product one-tenth of itself." For 
example, if the specific gravity is 1,015 and total number 
of ounces 40, then 15 X 40 = 600, + 60 = 660 grains of 
solids (or 330 grains, urea). 

In this supposititious case, 500 grains of waste solids 
(or more than 200 grains of urea) were retained on that 
particular day, i. e., if the patient were an adult, weighing 
from 150 to 160 pounds. Women excrete absolutely less 
than men; but not relatively, proportionate to their weight. 

It will readily be understood that in such a case as 
above described, efforts should at once be made to assist 
the organism in ridding itself of this burden of retained 
waste, and insure this desirable outcome by way of every 
possible channel of exit — kidneys, skin, liver and bowels. 

Irritability of Neck of Bladder. — It should not 
be forgotten that incontinence of urine, near the two ex- 
tremes of life, may often be due to irritation of the neck 



136 URIC ACID AND ITS CONGENERS. 

of the bladder, owing to the passage of a strongly acid 
urine loaded with urate crystals. 

In babes, of course, the urine is voided at any and all 
times, owing to the fact that the sphincter muscle at the 
neck of the bladder is yet undeveloped. At the stage of 
youth, however, this muscle, like the sphincter ani, has 
grown to sufficient strength, in the way of contractile 
power, to prevent the involuntary emptying of the bladder; 
though, of course, the previous "habit" of submitting to 
urinary pressure must gradually be overcome by a system 
of education. Nature will succeed in these cases, pro- 
vided there is no extraneous influence to prevent. Un- 
fortunately, such a hindrance to normal action is often 
seen in the constant irritation produced by the passage of 
minute irregularly formed crystals of uric acid in an over- 
acid urine. 

To determine, in a given case, whether the incon- 
tinence (or frequent urination) be due to irritation of this 
character, a brief examination of the urine will usually 
suffice. If the latter is over-acid and contains urate crystals 
in abundance, as shown by the characteristic "brick-dust" 
deposits, the diagnosis is readily established and the proper 
alkaline treatment may be instituted. 

Again, in advanced life, the sphincter muscle becomes 
more or less weakened, from years of constant usage; and, 
though incontinence may not result from this acid irri- 
tation, we usually observe that frequent urination becomes 
necessary to prevent the otherwise involuntary emptying 
of the bladder. The diagnosis is readily made from an 
examination of the urine, as already described. It should 
be remembered, however, that enlarged prostate is a 
frequent accompaniment of this condition, in elderly 



URINARY ANALYSIS. 137 

males. Nevertheless, the alkaline eliminative treatment 
will generally prove beneficial. 

Hepatic Torpor. — The characteristic brick-dust 
deposits in over-acid urine, is indicative of an attempted 
excessive excretion and is almost always just prior to an 
"explosion," — i. e., the effort on the part of Nature to rid 
the system of previously retained urates, — though this is 
not invariably true, for the excess excreted may be due to 
faulty metabolism: that is, an increased quantity of urates 
may be carried to the kidneys for excretion, owing to the 
failure of the liver to oxidize its normal proportion of uric 
acid (50 per cent.) into urea. The excess, in other words, 
is composed largely of uric acid that, under normal con- 
ditions, should be oxidized into urea by the oxidases of the 
liver. 

The ill effects of this form of hepatic insufficiency are 
most commonly met with in those who lead an indolent, 
luxurious life, or in those whose occupation keeps them 
within doors and subjects them to more or less mental 
strain and worry. There is generally present great de- 
pression of spirits and a general sense of weariness and 
inaptitude for effort of any kind. The sleep is sometimes 
restless, and on awakening in the morning the victim feels 
as tired and listless as on retiring the previous night. 

Familiar to every practitioner is the countenance of 
the "bilious" individual, his sallow, yellowish skin, dull 
eye, sodden tongue covered with a thick yellowish fur, 
offensive breath and complaints of nausea, lack of appetite, 
constipation, alternating with attacks of diarrhoea. All 
these clinical phenomena are doubtless due to inactivity of 
the liver, accompanied with an excess of unoxidized uric 
acid in circulation. 



138 URIC ACID AND ITS CONGENERS. 

Many people suffer periodically with the symptoms 
above enumerated and yet do not consider themselves 
sufficiently ill to consult a physician. They consider it as 
a matter of course that nature ordained they should not 
enjoy good health and spirits only at occasional intervals. 
Instead of presenting the matter to a physician, thus 
enabling him to treat their condition in a rational and 
scientific manner, the majority of these people proceed to 
treat themselves. Physic is resorted to every few days 
(which, at first, benefits them temporarily), and eventually 
the vicious "pill habit" is formed. Not until the urgent 
symptoms arise which force these patients to seek pro- 
fessional advice, do they finally realize the fact that they 
are not well, but actually ill. 

Should the urinary signs, above described, accompany 
the constitutional signs of hepatic insufficiency, the physi- 
cian may feel assured that the diagnosis of the uricacid- 
aemic stage of purin excess is well established, and that he 
is justified in recommending the proper treatment for that 
condition. 



CHAPTER XVI 



URIC ACID TESTS. 



r, 



Murexid Test. — To determine the presence of uric 
acid in the urine, by chemical means, the murexid test is 
probably the simplest, and is one of extreme beauty, to wit: 

A small portion of the urinary sediment, or the residue 
obtained by evaporating to dryness at a low heat over an 
alcohol lamp a few drops of urine in a watch crystal, is 
placed on a porcelain plate, a drop or two of nitric acid 
added to dissolve it, and the solution carefully evaporated 
to dryness over a spirit-lamp flame: a red residue remains. 
A drop or two of liquor ammoniae is added to this, when 
there promptly appears a beautiful purple color, which will 
gradually diffuse itself as the ammonia spreads. This in- 
dicates uric acid or the urates. 

The above method sometimes proves unsatisfactory 
owing to tardy results and a pink (instead of purple) color 
produced. It will be found by experience, too, that 
a slight excess of ammonia destroys the beautiful purple 
color. One of the most important precautions to be ob- 
served in performing this experiment, is to drop the 
ammonia upon the plate without at first allowing it to come 
into direct contact with the residue. 

Prof. Samuel E. Earp, of Indianapolis, recommends 
that a volatile salt of ammonia be used instead of a solution. 
The salt is placed on a metal plate and covered with the 
evaporating dish. The heat from the flame which is then 
applied underneath the plate, causes quick volatilization; 
and it will be found that the purple red (purpurate of 



140 URIC ACID AND ITS CONGENERS. 

ammonia) color covers the evaporating dish completely on 
its inner surface. 

Approximate Test. — For ordinary practical pur- 
poses the approximate amount of urates present may be 
determined as follows: 

Strongly acidulate some urine in a test-tube with 

hydrochloric acid and set aside for twenty-four hours. An 
examination, then, will reveal crystals of uric acid collected 
in the bottom of the container, also some on the sides and 
some floating on the surface of the urine. By testing the 
urine in question against a companion tube holding an 
equal quantity of normal urine and treated in the same 
manner, an approximate comparison may be made which 
will be accurate enough for ordinary purposes. 
"^J In the foregoing experiment, it should be understood 
that nearly the whole, if not all, of the uric acid thus made 
evident, is obtained from the decomposition of the urates 
with the consequent liberation of the acid. 

Heat and Acetic Acid Test.— The detection of an 
excess of uric acid in the urine/according to the following 
plan, is very simple: 

The testis best done by filling a test tube nearly full of 
urine and bringing the upper stratum to the boiling point; 
then add a few drops of four per cent, solution of acetic 
acid, boil again and set the test tube aside in a cool place. 
The crystals of uric acid will begin to form directly under 
the surface layer of the urine. The amount formed will 
give the relative quantity excreted, thus indicating the over 
production. When the amount of uric acid in the urine is 
normal, no precipitation of the acid can be effected by this 
method. 

While the above is not an absolute quantitative 
method for estimating the uric acid, it is one that is practical 



URIC ACID TESTS. 141 

and shows very quickly that there is overproduction, also 
the relative amount of overproduction from day to day. It 
can be made accurately quantitative by collecting the uric 
acid crystals on a weighted filter and reweighing, which will 
give the exact percentage of uric acid in excess of the normal 
amount. In this manner, and in a few hours, the exact 
quantity of uric acid can be estimated. 

Of course, when there is no excess of uric acid in the 
sample, it requires the use of a considerable quantity of one 
of the stronger mineral acids — sufficient to decompose the 
normal urates and thus set free the uric acid otherwise held 
in combination with the sodium — before the presence of 
the crystals is demonstrated. 

By applying this so-called "heat and acetic acid test" 
from day to day, or from week to week, as the importance 
of the case may indicate, it is very easy to determine with 
accuracy the perfection of enzymatic oxidation, or whether 
there is an increase or decrease in the perfection. 

, Heintz' Test. — A few years ago it was the common 

practice in the laboratory to employ Heintz' test for the 
quantitative estimation of uric acid, but it has since become 
the custom to resort to the more accurate (though more 
complicated) method of Hopkins or Folin./ The "gravi- 
metric method" recommended by Heintz is usually applied 
as follows : 

Take 200 cubic centimeters (nearly half a pint) of 
urine, and add to it twenty cubic centimeters (six fluid 
drachms) of hydrochloric or nitric acid. Set aside in a cool 
place, as a cellar, for twenty-four hours (better forty-eight 
hours), at the end of which time the highly colored uric acid 
crystals will be found adhering to the sides and at the bot- 
tom of the beaker glass. Collect these precipitated uric 



142 URIC ACID AND ITS CONGENERS. 

acid crystals on a previously weighted filter and wash 
thoroughly with cold distilled water. Dry the filter and 
crystals in any hot place, as in a desiccator, at a tempera- 
ture of 212° F.; and then weigh. The weight of the two, 
minus the weight of the filter, will be the weight of the uric 
acid in 200 cubic centimeters of urine — excepting, of 
course, the small portion retained in the acid and washings. 

In employing this method, if albumin be present, it 
should first be removed. Moreover, the urine should 
always be filtered before applying the test, for otherwise 
subsequent filtration is very difficult. 

Harley's Test. — This is a very delicate qualitative 
test^and is most conveniently applied as follows: 

In a solution of sodium or potassium carbonate dis- 
solve a portion of the suspected uric acid precipitate, and 
place a drop or two of the resulting solution on paper. Add 
to this a solution of silver nitrate. If a distinct gray stain 
promptly occurs it is positive evidence of the presence of 
uric acid or urates. ^ 

Schiff's Test. — This is very similar to the foregoing 

test, and is best employed as follows: 
p— A piece of filter paper is moistened with a solution of 
nitrate of silver, and a drop of a solution of the suspected 
uric acid deposit in sodium carbonate is added. Owing to 
the reduction of the oxide of silver, a brownish black color 
develops, which is a certain indication of the presence of 
uric acid. If there is only 0.002 milligramme of uric acid 
present, a yellow color is obtained instead. 

Dimmock and Branson's Method.— For the rapid 
quantitative estimation of uric acid, the following method 
devised by Dimmock and Branson is considered quite 
satisfactory: 



URIC ACID TESTS. 143 

To ioo cubic centimeters (3J fluid ounces) of urine 
is added one gramme (16 grains) of lithium carbonate 
(Li 2 C0 3 ). After boiling, for about three minutes, in a con- 
ical flask (Erlenmeyer) of about 100 cubic centimeters 
capacity, the liquid is filtered while hot to remove the 
precipitated earthy phosphates, etc., which are washed 
with a little distilled water until the filtrate measures ex- 
actly 100 c.c. To 50 c.c. of the filtrate, which contains 
uric acid as lithium urate, 5 grammes of ammonium 
chloride are added, shaking the liquid, until dissolved. 
After three minutes, the contents of the flask are warmed 
to 120 F., so as to secure a uniform aggregation of the 
precipitated ammonium urate. The whole is now poured 
into a tube, graduated in parts per thousand of uric acid, 
and deposition allowed to take place, the reading being 
taken after four hours have elapsed. 

Microscopic Examination. — Without entering into 
details, it may be said that the presence of uric acid as such 
is generally easily recognized by the microscopic peculiar- 
ities of its crystals, which in their commonest form may be 
said to be "lozenge-shaped." It should be remembered, 
too, that the crystals are always colored yellowish red, 
being with their salts the only urinary deposits thus stained. 
Therefore, when a sediment is examined, the crystals of 
which are thus colored, it may, without hesitation, be con- 
sidered as composed of uric acid or its combinations. 

Should a crystalline deposit, examined under the 
microscope, still remain of doubtful character, it can be 
shown to be uric acid, whenever it will respond as follows : 

(a) Insoluble in cold or hot water, but readily dis- 
solves in the alkalies — soda, potash, or ammonia; then, if 
the alkaline solution thus produced, be treated with an 



144 URIC ACID AND ITS CONGENERS. 

excess of acetic acid, the typical "lozenge-shaped" forms 
will crystallize out in a few hours. 

(b) The sediment placed on a glass slide responds to 
the murexid test. 

Occasionally we meet with "dumb-bell" crystals of 
uric acid which have the characteristic shape of oxalate of 
lime crystals. They may be distinguished from the latter, 
however, by their larger size, their darker color, and their 
solubility in alkalies. 

The Complicated Tests. — The three tests for the 
quantitative estimation of uric acid, which are doubtless 
the most exact, are the Hopkins' Method, the Folin's 
Method, and the Ludwig-Salkowski Method. One or the 
other of these is now employed in expert laboratory work; 
but it is practically impossible for the physician to utilize 
any of them. The details of each method may be found 
published in full in special treatises on urinary analysis. 

The Hopkins' Method furnishes results which are as 
accurate as those obtained with the older method of Lud- 
wig-Salkowski, and has the advantage of greater simplicity. 
" It is based upon the fact," says Simon, " that uric acid can 
be completely precipitated from the urine by the addition 
of certain ammonium salts. Insoluble acid ammonium 
urate thus results, which is transformed into the free acid, 
and this estimated either gravimetrically or by titration 
with a solution of potassium permanganate of known 
strength." 

Folin's Method is a recent modification of the above 
and is being adopted by the majority of chemical investi- 
gators; it is sometimes spoken of as the "Folin-Hopkins 
Method," or "Folin's Modification of Hopkins' Method." 

The Uricometer. — A glass instrument has been 
devised by Ruhemann, of Germany, for the ready deter- 



URIC ACID TESTS. 145 

mination of the quantity of uric acid in a given sample of 
urine. He explains his method as being simple, quick and 
practical, as follows: 

At the bottom of the instrument sulphuric acid is 
placed, to which is added a solution of iodine, 1.5 gm., 
with which has been titrated potassium iodide, 1.5 gm., 
alcohol, 15 gm., and distilled water, 185 gm. Urine is then 
dropped, one drop at a time, shaking after each addition, 
until the solution is pale pink. This, upon the last shaking, 
becomes milk white. 

With each instrument, detailed explanations of the 
above reaction are given. The sides of the uricometer are 
marked, the level of the mixture showing the percentage 
of uric acid in the sample examined. 

Hall's Purinometer. — I. Walker Hall, M.D., of 
Manchester, England, has invented a glass instrument 
(simpler in construction than Doremus's ureameter) for 
the purpose of estimating the amount of purins in the 
urine, or elsewhere. It consists essentially of three parts, 
viz.: (1) A closed, graduated tube; (2) A stop-cock with 
a bore of the same diameter as the upper tube; (3) A 
small glass reservoir of known cubical capacity. 

Printed directions for its intelligent use accompany 
each instrument. The "purinometer" was made for Hall 
by Goetze, of Leipsic, and may be obtained from Messrs. 
Gallenkamp, Sun Street, Finsbury, England. 

A Simple Test. — Quantitative estimation of uric 
acid may be performed by adding a teaspoonful of con- 
centrated hydrochloric acid to three fluid ounces of urine 
and allowing it to stand for forty-eight hours in the dark. 
The uric acid deposits are then dried and weighed. 



CHAPTER XVII. 

bright's disease. 

Definition. — The term " Bright's disease" has been 
applied, since 1827, to renal disorders characterized by 
various histological changes in the kidney substance, which 
give rise to the three classic symptoms described by Bright 
— albuminuria, dropsy and uraemia. It has sometimes 
been defined as a disease characterized by degeneration 
of the kidneys, whereby the excretory function is so im- 
paired that urea and the urates are not satisfactorily elimi- 
nated from the blood. 

Congestion. — As the kidney is composed of delicate 
tissue highly vascularized, it is naturally subject to the 
same sudden external influences that cause congestion of 
other internal organs and specialized tissues, and which 
may develop an inflammation. Therefore, congestion, or 
acute inflammation of the kidney may occur as in any 
other highly vascularized tissue, brought on by exposure 
of the body to cold and dampness, thus causing contracted 
surface capillaries and a flux of blood to the deeper organs 
— to the kidney for instance, after lying prone on the back 
on damp ground. 

True Bright's.— Though a congestion or inflam- 
mation, such as we have just described, may render the 
kidney more liable to Bright's disease thereafter; yet, in 
itself, it can hardly be classed as true Bright's, since any 
of the mucous or serous membranes as well as other gland- 
ular organs may become affected in this way by such 
accidental causes. By true Bright's is meant those tissue 



BRIGHT'S DISEASE. 147 

degenerations or histological changes, to which the kidney 
alone is rendered liable, owing to its anatomical position 
and physiological duty as an excretory organ. In this 
latter capacity, the kidney is subject to insidious vascular 
influences which interfere with its work as a dialyzer and 
eventually give rise to anatomical changes in its tissue. 

It will be seen, then, that the disabled or crippled 
kidney in "true Bright's," is the indirect result of the 
delicate and dangerous task it has to perform in elimi- 
nating waste tissue products and accidental toxins from 
the blood. Being a process of change, slow in its develop- 
ment, Bright's disease is usually "chronic"; though, of 
course, under specially aggravating circumstances, it may 
be subacute or even acute. 

Renal Dialyzer. — By means of the glomeruli of the 
Malpighian body and the epithelium lining the tubules, 
the kidney serves as a renal dialyzer. From the blood 
brought to it, it dialyzes in aqueous solution (the urine) 
the greater part of the excretory products of the human 
organism, resulting from the wear and tear of the body 
cells, the chief and most important of which are (i) the 
intermediary and end products of nitrogenous metabo- 
lism and (2) the soluble mineral salts. 

It also dialyzes the overplus products of digestion, 
not utilized by the organism; the various extraneous 
matters introduced occasionally, such as poisons, drugs, 
etc.; and the ptomaines and other products of decom- 
position or fermentation, absorbed into the circulation 
from the intestinal tract. Of the total amount of water 
thrown off daily by the human organism, at least fifty per 
cent, is excreted by the kidneys in the form of urine, which 
contains in solution or suspension the various substances 
alluded to. 



148 URIC ACID AND ITS CONGENERS. 

Specialization. — It has been discovered that the 
renal dialyzer, in its entirety, is so constructed that it acts 
differently than a mere mechanical apparatus; though, of 
course, the epithelial membrane is subject to the same 
mechanical influences in the way of pressure, etc., (due 
to arterial tension) as any other dialyzing membrane 
would be. The epithelial cells lining the tubules not only 
serve as a mechanical filter, but, like the nucleated cells of 
the secretory organs, they possess the power of apparent 
selection. For instance, it has been found that organic 
substances such as uric acid are eliminated by the rodded 
epithelium of the tubules, while the glomeruli chiefly 
separate the water and inorganic salts normally present in 
the urine. This specialization in the work of the cells, 
however, is probably due to the known difference in their 
structure, one form of cell permitting certain substances to 
dialyze or filter through, while the other form does not. 

Localization. — It will at once be seen that these 
delicate cells in their dialyzing capacity will become 
differently affected, according to their special duty; one, 
in its work of osmosing water and its contained salts, the 
other in its work of osmosing organic substances. 

Inasmuch as the glomeruli are minute vessels belong- 
ing to the vascular system, they will naturally be chiefly 
affected by circulatory influences in the way of pressure or 
lack of pressure, and will suffer in sympathy with the 
heart and its vessels — i. e., becoming disturbed coinci- 
dently with cardiac troubles, arterio-sclerosis, etc. On 
the other hand, any trouble with the epithelium of the 
tubules must be ascribed to the irritation arising from its 
work in eliminating the organic toxins — either from over- 
work, or from the necessity of eliminating imperfectly 



BRIGHT'S DISEASE 149 

catabolized toxins which are dialyzed with greater diffi- 
culty. 

In chronic Bright's disease, according to Bate (Cf. 
The Lancet-Clinic, Oct., 1905, p. 412), "the glomeruli 
long remain normal after the rodded epithelium of the 
tubules have undergone changes, thus showing that the 
organic toxins (uric acid, etc.), eliminated by these rodded 
epithelial cells, give rise to the tubular changes prior to the 
vascular changes. Therefore, not only must the cause of 
this metabolic hindrance be removed, but the toxins al- 
ready in the system must be eliminated in some non-ir- 
ritative form." 

^Etiology. — Various substances, accidentally intro- 
duced into the organism, will, of course, in their passage 
through the dialyzing cells, irritate the renal epithelium or 
glomeruli and may produce inflammation and degenera- 
tive changes characteristic of Bright's — drugs like can- 
tharides and lead, for instance. But in the common forms 
of Bright's disease, the irritation is more gradual and, in 
the great majority of cases, is caused by the overplus ex- 
cretion of organic products of nitrogenous catabolism — - 
generally imperfectly oxidized. Or, it may be due in 
some instances, of course, to absorption of toxins from the 
intestinal tract. 

Minkowski found that 0.5 gramme of adenin, ad- 
ministered daily to dogs, produced malaise, vomiting, and, 
after five or six days, death. Before death, the urine of 
these animals contained albumin, casts, and epithelial 
cells; and, after death, the kidneys showed inflammatory 
changes and uric acid deposits. Though this is, of course, 
a much more rapid process than that which is noted in 
Bright's disease, nevertheless it serves to illustrate how 



150 URIC ACID AND ITS CONGENERS. 

irritating to the epithelial cells are the suboxidized pro- 
ducts of purin metabolism. 

According to Schmiedeberg, the effects of the purin 
derivatives, in considerable dosage, is to increase reflex 
irritability, and, ultimately, to cause complete tetanus or 
even paralysis. The muscles may become permanently 
contracted, passing into a condition of coagulation similar 
to that produced by heat and cold; while the action on the 
kidney is seen in the marked diuresis. 

Vaughan, in his "Cellular Toxins" (page 346), states 
that hypoxanthin and most of the other purins coagulate 
muscle, and that their diuretic action parallels this effect. 
He believes that the increased reflex irritability which they 
cause is due to the nitrogen groups (as with ammonia 
compounds), but that the action upon muscles and kidneys 
is peculiar to the purin molecule. 

This same author (page 344) again states: 'The 
actual amount of uric acid eliminated may be considera- 
bly less than that actually carried to the kidneys to be elimi- 
nated, since the kidney may be incapable of effecting the 
complete excretion. In this case, deposits of uric acid 
will occur either in the joints (as in rheumatism), or in 
the kidneys, as in adenin poisoning or in the infarcts of 
the new-born (Spiegelberg)." He also believes that "the 
purin bases may be looked upon as undergoing changes 
similar to those of uric acid." 

Rachford, in "Neurotic Disorders of Childhood" 
(p. 79), attributes kidney disease to the irritant action of 
the purin bodies. He further says (p. 83) : 'The gastro- 
intestinal canal is probably the most important channel 
through which the purin bodies may be eliminated, when 
there is defective excretion through the kidneys; this fact 



BRIGHT'S DISEASE. 151 

is quite empirical and is based on the accumulated testi- 
mony of the medical profession for many years. The value 
of laxative medication in these cases, however, is probably 
not entirely due to the fact that in this way the absorption 
of exogenous or intestinal purins into the circulation may 
be largely prevented, but it is also probably due to the 
fact that the intestinal canal, by proper cathartic medica- 
tion, may be stimulated to the more rapid excretion of 
endogenous purins and other poisons circulating in the 
body media." 

Croftan, after numerous experiments, has come to 
the conclusion that the purin bases are capable of pro- 
ducing cardio-vascular changes in those forms of nephritis 
in which retention of excrementitious substances precedes 
the lesions of the heart and arteries. He believes that the 
purin bases are the primary factor in the causation of 
"gouty" kidney. In the "lead" form of interstitial 
nephritis, the toxic action of this metal is either the same 
as that of the purin bases, or it can cause changes in the 
organism which lead to the formation of these bases. The 
same toxins may simultaneously produce both nephritis 
and arteriosclerosis. From his investigations, this author 
concludes that the purin bases play an important role in 
the production of the cardio-vascular changes observed in 
all forms of nephritis, excepting the chronic indurative 
form sometimes seen as the result of senile arteriosclerosis. 

Experiments Upon Rabbits. — To determine the 
effect of continued daily injections of purin bodies in 
rabbits, I. Walker Hall, of England, performed a very 
interesting experiment. Four young rabbits were kept 
under observation for fifty days. In two of the rabbits, 
daily injections of a solution of hypoxanthin were given 



152 URIC ACID AND ITS CONGENERS. 

during this time, and, in the other two, a solution of guanin. 
At the death of the animals, post-mortem in the first two 
showed the cortex of the kidneys to be very pale, with 
little distinction between the two zones. In both of the 
other animals, the kidneys showed degenerative changes 
in the cells of the tubules, marked hyperaemia, and a com- 
mencing proliferation of the intima of the smallest arter- 
ioles; but no interstitial nephritis, and no glomerular 
changes, — as yet. 

Deductions. — If we have properly interpreted the 
findings brought to light from the many experiments held 
by different investigators, it would seem to have been con- 
clusively demonstrated that the rodded epithelium of the 
renal tubules is the first tissue to be affected in a beginning 
degeneration of the kidneys, due to suboxidized metabolic 
products — which, of course, is not recognized as Bright's 
disease, until the process has become sufficiently advanced 
to give rise to the well-known objective signs. It is im- 
portant, therefore, that we should know what causes this 
first injury, and thus be enabled to remove such cause 
before the kidney becomes seriously damaged. In short, 
our attention should be directed toward certain symptoms, 
which precede those indicative of an advanced stage of 
some renal disorder. 

As the rodded epithelium of the tubules is known to 
be specially engaged in dialyzing from the blood the organic 
substances present in the urine : — the products of nitrog- 
enous catabolism — it is evident that the primary trouble 
is some fault of metabolism, and that the irritant is either 
a purin or ureid (or both), or urea itself. It can hardly be 
urea, since this product continues to be dialyzed (i. e., 
does not become retained) until the epithelium of the tu- 



BRIGHT'S DISEASE. 153 

bules has become degenerated to an alarming extent and 
has involved the surrounding tissues, so that even water 
is imperfectly osmosed. Urea is evidently the complete 
end product of nitrogenous catabolism; and it is the best 
form which Nature has yet succeeded in evolving, for the 
purpose of being easily dialyzed (without causing irrita- 
tion) by the delicate epithelium lining the convoluted 
tubules. 

It is evident, therefore, that the irritation of the epithe- 
lial cells, at the outstart, is not due to the osmosis of urea, 
but to the more difficult osmosis of the ureids, which the 
oxidase of the liver and the intracellular ferments of the 
tissues have failed to oxidize into urea, thus leaving a con- 
siderable quantity of unoxidized nitrogenous waste, in the 
form of uric acid, to be dialyzed by the kidney epithelium. 
It is much like asking the gastro-intestinal membrane to 
absorb food products that have been imperfectly digested, 
or the stomach to digest food particles that have been im- 
perfectly masticated: irritation results in both instances. 

A certain proportion of ureids, in the form of uric acid 
is capable of being dialyzed through the tubularepithelium 
without apparent harm (just as a small proportion of im- 
perfectly masticated food may be digested); but, if the 
proportion be increased beyond this certain point, or if 
ureids in some unusual form (allantoin, for instance) be 
present, it will sooner or later result in irritation. This 
fact, indeed, is shown in the experiments upon animals, 
when purins introduced in considerable amount lead to the 
formation of more uric acid than can be excreted, resulting 
in inflammation of the tubular epithelium and deposits of 
urates in the canaliculi and elsewhere. 

It is known that continued ingestion of alcohol inter- 
feres with the oxidative function of the liver and results in 



154 URIC ACID AND ITS CONGENERS. 

an excess of unoxidized uric acid in circulation — especially 
if purin-containing food substances be eaten freely at the 
same time. At first, under such circumstances, the kidneys 
succeed in eliminating the excess of uric acid, as may be 
observed by urinalysis; but, eventually, if the abuse be 
kept up, the irritation of the epithelium leads to degener- 
ation of the renal epithelial cells and they become unable 
to dialyze the urates brought to them, and finally the urea 
itself. The same results obtain whenever the liver fails to 
perform its metabolic function (oxidation into urea) 
properly, from whatsoever cause. The ultimate conse- 
quence is likely to be Bright's disease. 

The Three Stages. — It will be seen that the kidney 
of chronic Bright's disease, as well as the "gouty" kidney, 
presents evidence of passing through the three stages of 
purin excess. In the "uricacidaemic" stage, the kidney is 
simply embarrassed in its work, owing to the obstruction 
of the capillaries and the consequent variation in the 
mechanical pressure upon the dialyzing membrane. We 
have a "torpid" kidney as well as "torpid" liver. 

In both the rheumatic and uricacidaemic stages, the 
kidney is subjected to its greatest irritation during an 
"explosion" of the urates, when the dialyzing capacity of 
the rodded epithelium of the tubules is strained to its ut- 
most. Not many such "explosions" should be allowed to 
occur, before proper measures be taken to prevent the in- 
evitable damage thus threatened. Indeed, we should not 
wait for any further evidence of a possible Bright's disease. 

The third, or gouty stage, is that in which the urates 
can no longer be dialyzed, except very imperfectly; are 
retained and become deposited, either in the body else- 
where or in the kidney itself, finally becoming crystalline. 



BRIGHT'S DISEASE. 155 

The kidneys of uricacidaemic and rheumatic patients 
become more or less injured at the time of every "ex- 
plosion" of the urates by way of the urine; though, in 
many instances, the kidneys will escape for a time, owing 
to the explosions taking place in the joints or elsewhere. 
The tendency of nature, however, is to rid the system of the 
excess if possible ; and, if she be left unaided at such times, 
a heavy burden is likely to be put upon the kidneys — one 
that may prove disastrous to the delicate epithelial cells. 
It is right here that the physician is given oppor- 
tunity to prove the worth of his calling, by apportioning 
out the work of excretion, giving the bowels -a due share, 
and lightening the work of the kidneys by presenting the 
urates in greater dilution and in non-irritative form. At 
the same time, efforts should be made to aid the liver in its 
work and stimulate a more active body metabolism, thus 
leading to a fuller oxidation of the products of nitrogenous 
catabolism — i. e., into the end product, urea. Overin- 
dulgence in purin-containing foods and drinks, should of 
course, be prohibited. • 

An Early Sign. — In the opinion of Hobart Amory 
Hare, as expressed in his " Practical Diagnosis, or The Use 
of Symptoms in the Diagnosis of Disease" (p. 408): 
"Often an excess of uric acid in the urine antedates the 
development of chronic contracted kidney." 

The moral to be derived from this study is, that appro- 
priate eliminative treatment should be begun at the pri- 
mary stage when "uratic explosions" are common — thus 
preventing further damage to the renal dialyzer and a 
probable Blight's disease which may ensue. 



CHAPTER XVIII. 



INFANTS AND CHILDREN. 



Uric Acid Infarcts. — The earliest stage in life, in 
which disordered conditions of the system due to uric acid 
are manifest, is in the newly-born infant with uric acid in- 
farcts of the kidney. Though these infarctions, according 
to Koplik (Diseases of Infancy and Childhood, 619), "are 
found in the kidneys of over one-half of the infants who die 
in the first weeks afterbirth," — and, probably, also occur 
in the majority of all new-born infants; yet, in the opinion 
of most authorities, the serious symptoms resulting from 
pathologic changes in the kidneys, are principally met with 
in those cases in which a "gouty" ancestry can be traced. 

In discussing the appearance of these infarcts, Fen- 
wick and Lewis (Disorders of Digestion in Infancy and 
Childhood, 17) state that, when the kidney is examined 
under the microscope, "the straight tubules are found to be 
blocked by opaque granular cylinders, which, under a high 
power, are seen to be composed of a vast number of 
spheroidal crystals." Considerable discussion has taken 
place concerning the exact composition of these crys- 
talline deposits: Virchow maintaining that they consist of 
urate of ammonium, while other authorities (Parrot, West) 
consider them to be either uric acid or urate of sodium. 

The presence of these infarcts is generally attributed 
to the sudden alteration in the blood circulation of the 
newly born and the consequent plus excretion of nitrog- 
enous metabolic waste products in the kidneys. Inas- 
much as little water is consumed during the first few days 



INFANTS AND CHILDREN. 157 

of extra uterine life, these products are not flushed out; 
but, on the contrary, tend to settle in the pyramidal portion 
of the kidney in the straight lining tubules. In the words 
of Virchow: "It is quite common to see reddish or yellow- 
ish deposits, or even brownish streaks, which microscopical 
examination shows to be uric acid crystals blocking the 
straight urinary tubules." (Cf. Keating's "Cyclopaedia of 
the Diseases of Children," Vol. I, p. 70). 

Concerning this point, we note the following in 
Graetzer's "Practical Pediatrics," page 34, (translated 
from the German by Sheffield, 1905): "Post mortem 
transverse section reveals here a yellowish-red streak. 
This uric acid infarct usually disappears after the child 
has consumed more fluid, and is entirely eliminated after 
two or three weeks. At times, however, it is of longer 
duration: uric acid and ammonium urate crystals are 
retained in the lumen of the tubules, of the papillae and 
renal pelvis as small reddish-yellow granules, which, after 
having produced certain disturbances, become visible in 
cloudy urine." 

Symptoms. — "The urine of the first few days of life," 
says Holt (The Diseases of Infancy and Childhood, 639) 
"often shows a deposit of urates or uric acid in the form 
of a reddish-yellow stain upon the napkin. The reaction 
of the urine at this time is usually strongly acid." 

If the young nursling is restless while urinating, cries 
aloud, strains hard and passes but little urine, uric acid 
infarct must always be thought of. The wet portions of 
the diapers are generally found to be darker in color than 
usual: it is sometimes observed that the margins of these 
spots have a reddish shade and are covered with reddish 
granules. Not until these are found is the diagnosis 



158 URIC ACID AND ITS CONGENERS. 

certain, as the other symptoms may be caused also by 
cystitis for instance. 

Uric acid infarct may also give rise to redness of the 
prepuce or the internal surface of the labia as a result of 
irritation. In older children these symptoms usually do 
not indicate the presence of a uric acid infarct, but of the 
existence of newly formed uric acid concretions, which are 
undoubtedly formed in their development by residues of 
the former. Uric acid infarcts also give rise to nephritis. 
"It is therefore advisable," says Graetzer, "to aid the 
elimination of persistent uric acid infarcts as soon as pos- 
sible by means of large quantities of water." 

A Clinical Picture. — E. J. Lorenze, of New York, 
reports a typical case of uric acid infarcts, in an apparently 
healthy child, born of a young Irish woman, which, at the 
end of the first week after birth, began to cry too much. At 
the end of twenty-four hours (the crying having continued 
almost constantly), fever developed and slight gastric 
disturbances, consisting of occasional vomiting. At this 
time, pink stains appeared on the child's napkins. At 
every act of micturition, the napkin had a salmon-colored 
stain, sometimes small and sometimes rather large. This 
stain was at once recognized as the "brick-dust deposit," 
and plenty of water was immediately ordered to be ingested 
as recommended above by Graetzer, by Holt, and by other 
pediatric authorities. The infant received all the water it 
could hold. It soon became evident, however, that the 
treatment would have no effect. The child became worse; 
temperature rose to 104 F.; the face was anxious in ex- 
pression at all times. The legs were flexed, and often the 
thighs were flexed on the abdomen. The abdomen was 
usually hard, but no special tenderness on pressure was 



INFANTS AND CHILDREN. 159 

noticed. Urine continued to show the brick dust stains. 
After a week of suffering the child died. 

About fifteen months later, Lorenze delivered this 
same woman of another child, which resembled the former 
in almost every respect. In about five days, the infant 
began with brick dust deposits on its napkin, and suffered 
symptoms similar in all respects to the other child. In 
addition to the water in this case, the alkaline lithia salt, 
elsewhere described in this work, was administered. The 
mother received a teaspoonful in a glassful of hot water 
three times a day, and ten grains were administered to the 
infant three times a day — the child nursing at the mother's 
breast. "In two days," says Lorenze, "all stains dis- 
appeared from the napkins, and the child developed and 
remained normal in every respect." 

. The unfortunate outcome of the treatment in the first 
case, and the speedy and satisfactory results obtained from 
the use of an alkali in this second case, indicate that the 
trouble in both instances was doubtless due to the presence 
of uric acid infarcts, and that the kidneys not only needed 
to be flushed out with water, but required assistance in the 
way of an alkaline solvent and eliminant. 

Uricacid^mic Signs. — In children, whose youthful 
organisms become burdened with an accumulation of 
urates in excess, symptoms referable to the uricacidaemic 
stage are those which are most commonly observed. The 
reason for this preponderance of uricacidaemic over rheu- 
matic or gouty signs is easily explicable. The difference 
between a child and an adult, in the ability to quickly rid 
the system of uric acid by way of the proper channels, is 
readily understood. Owing to the active bodily metab- 
olism and rapidity of oxidation in children, due to their 



160 URIC ACID AND ITS CONGENERS. 

play out of doors, and with their eliminative functions un- 
checked by faulty kidney action (as is so often the case with 
adults), it will at once be seen that the excess of waste 
products of the uric acid type do not remain long in the 
body. On the contrary, they simply produce their tran- 
sient effects while en route through the blood, and are then 
excreted. Generally, there is no storing up of urates in the 
organs and tissues as is the case later in life. 

During infancy, uricacidaemia is not of frequent occur- 
rence due, of course, to the purin free diet; but, later in 
childhood, when meat soups, coffee and tea are given free- 
ly, we begin to get first diseases of the uricacidaemic type, 
and later those of the rheumatic. Chief among the dis- 
orders of the first class, due to the presence of urates in the 
blood of children, may be mentioned, according to Wheeler 
{Brooklyn Medical Journal, ]une, 1905): "migraine, con- 
vulsions, epilepsy, mental sluggishness, albuminuria and 
asthma." 

In the opinion of this author, girls suffer more than 
boys from these disorders, owing to their comparative lack 
of physical exercise. He believes, too, that the children of 
the rich develop these disorders much more than the chil- 
dren of the poor because of their being reared in luxury and 
allowed too much strong coffee, tea, rich soups and an 
excessive amount of meat. They are housed too much. 
Music, French, and German lessons keep them indoors 
when they should be playing in the open air. 

"As a type of such disorders," says he, "a child will be 
found anaemic; subject to headaches (of the persistent or 
migrainous type); capricious in appetite; perhaps over 
weight for its age, but with flabby flesh, circulation poor, 
extremities cold, nervous in speech and manner, and some- 



INFANTS AND CHILDREN. 161 

times showing choreiform movements: this, too, in a 
class of cases, which, although anaemic, bear iron badly." 
The urine, says Holt, is scanty, frequently pale, and in 
many cases contains an excess of uric acid. 

Drummond, in the Lancet, 1897, describes an aggra- 
vated condition of uricacidaemia in the young. "In some 
cases," he says, "there is a persistent headache in the 
frontal or vertical region, loss of appetite, constipation, 
anaemia and loss of flesh. The temperature of the body is 
low, and for several weeks at a time may remain below 
normal. The heart action varies. It is sometimes rapid, 
but more often slow. It is not uncommon to have a pulse 
of forty or fifty, although the patient is nervous in manner. 
The pulse tension is raised. The hands and feet are gener- 
ally cold. In some cases, sudden attacks of giddiness oc- 
cur which are difficult to distinguish from slight epilepti- 
form seizures. The knee-jerk, as a rule, is distinctly 
lessened and may be absent. A sluggish habit of mind 
and body may be noted along with other character traits 
foreign to the patient." 

The so-called "night-terrors" of children is another 
condition due to uricacidaemia, in the opinion of Wheeler, 
and may be classed with the paroxysmal neuroses, mi- 
graine and petit mal. This condition, he thinks, often 
alternates with migraine in the same patient, and like most 
other diseases under discussion is found in children who 
are nervous and excitable and come of rheumatic parents, 
— parents who have also produced weak-minded or epi- 
leptic children. In children of susceptible nervous systems, 
"convulsions" may take the place of an attack of mi- 
graine; in fact, this may be said to be the rule in very 
young children. 



%r- 



162 URIC ACID AND ITS CONGENERS. 

Cyclic Vomiting. — That nausea and vomiting is a 
frequent indication of infantile uricacidaemia (as it often 
is of this same stage in the adult), may be noted in the two 
cases of uric acid infarcts, with brick dust stains on the 
napkins, reported by Lorenze, in which this symptom was 
one of the first to appear and remained constant. The 
importance of examining the urine, in cases of cyclic 
vomiting, is shown by Holt (p. 328), who states that the 
following interesting observation upon the uric acid ex- 
cretion in one of his patients, was made by Dr. C. A. 
Herter — all the results being based upon the twenty-four 
hours' urine; to wit: 



Urea Uric Acid Ratio of Uric 
Grammes Grammes Acid to Urea 



Time Taken 

Before the attack 

(normal) 13.606 0.251 1 to 54 

First Day ! 7*249 0.110 1 to 157 

Second Day 12.023 0.091 1 to 132 

Third Day ll -7 1 3 °- 2 34 J to 5° 

Several weeks after- 
ward (normal) I 5-°4° 0.283 1 to 53 

Hematuria. — In the opinion of Holt (p. 104), the 
blood carried from the kidney, in these cases, is some- 
times due to the irritation of uric acid infarctions, and may 
have nothing to do with the general hemorrhagic disease. 

Lithiasis. — The authoritative statement is made in 
the American Text Book of the Diseases of Children, 970 
(edited by Louis Starr, M.D., Philadelphia) that urine 
loaded with uric acid, urates, oxalates and phosphates, 
may cause an incontinence as well as irritable bladder; 
hence the urine in such cases should always be examined. 



INFANTS AND CHILDREN. 163 

The following significant statement is also made 
(p. 978): "Lithiasis is the deposition of certain solids of 
the urine in the urinary tract, any portion of which, from 
its beginning in a Malpighian capsule to its terminal ex- 
pansion (the bladder), may be the seat of such deposits. 
The sediments thus precipitated include uric acid and its 
compounds as the most common ingredients. They may 
be so minute as to be barely visible to the naked eye, con- 
stituting sand or gravel; or they may be a couple of inches 
or more in diameter, when they are spoken of in common 
language as stones in the kidney or bladder. The uric 
acid sediments are often found in the shape of red sand in 
the very first urinary discharges of the new-born infant. 
If, on examination, the urine is found highly acid in re- 
action, depositing uric acid sediments, the treatment is 
principally by alkalies." 

"It is admitted/' says Keating in his work (I-597), 
"that the urine of infants is richer in uric acid than that of 
adults. The uric acid infarctions of Virchow, the urates 
of sodium and ammonium, constituting the grit found in 
the kidney tubules, the brown dust on the napkins, which 
is shown by the microscope to be mostly formed of uric 
acid, all point to a congenital or inherited tendency to pro- 
duce this substance in excess. This excess may be positive 
or relative — positive in proportion to all other ingredients; 
and relative, in that other ingredients may be deficient. " 

Albuminuria. — Albuminuria may be a symptom due 
to uricacidaemia. With a more careful examination of 
the urine in children of late, we find albuminuria a more 
common condition than was formerly thought. It is very 
common at puberty. It very often follows an attack of 
migraine, and is due to the increased blood pressure 
incident to the collaemia. 



164 URIC ACID AND ITS CONGENERS. 

Asthma. — "Again," says Wheeler, "asthma is a con- 
dition which is comparable to an attack of migraine in the 
suddenness of its onset. In children asthma runs a some- 
what different course than in the adult. It never occurs 
as an independent condition, but may precede, accompany 
or follow a bronchial catarrh." A rheumatic parentage 
can also usually be traced in these cases. 

Rheumatic Signs. — While diseases of the uricaci- 
daemic stage are by far the most common in children; 
nevertheless, if the rules of dietary are violated day after 
day, or metabolism reduced by some intercurrent disease 
(as scarlet fever), then we may get a storing up of uric 
acid with development of diseases of the rheumatic type. 
Principally among the latter, says Wheeler, " are rheuma- 
tism, gout (rarely), adenoids, nasal-pharyngeal catarrh, 
chronic bronchitis and eczema." 

"Though there is a tendency in some quarters," 
says this author, "to class rheumatism among the germ 
diseases, nevertheless, I think we cannot rule out uric acid 
as a predisposing cause. Exposure to cold throws down 
the excess of urates in the blood into the joints and tendon 
sheaths, then with a lessened resistance of the tonsils, or 
naso-pharyngeal mucous membrane, a port of entry is 
given to a micrococcus which may be normally present 
and harmless in the oral cavity, but which becomes active 
in the blood with the production of toxins causing symp- 
toms of chills, fever and inflammation of the joints. 

In childhood, the joints are bathed in a more liberal 
amount of alkaline fluid than is the case in the adult, and 
even though the alkalinity may be so greatly reduced and 
the circulation of blood become so sluggish through cold 
as to cause a temporary deposit of uric acid or the acid 



INFANTS AND CHILDREN. 165 

urates, yet with the activity of metabolism these would be 
quickly redissolved and pass again into the blood to be 
excreted." For this reason, true gout is a disease almost 
unknown in childhood, though occasionally an isolated 
case is reported. 

Adenoids, naso-pharyngeal catarrh and chronic 
bronchitis are other diseases of childhood depending in 
part, if not wholly, on the uric acid tendency. Concerning 
the first mentioned, Mackie, of Nottingham, England, 
says: "I scarcely see a case of adenoids but where there 
is an arthritic or migrainous parentage." 

The frequency of pharyngitis, laryngitis and bronchi- 
tis in rheumatic adults, has frequently been noted. 
'These same conditions," says Wheeler, "occur in child- 
hood, but are not so constant an accompaniment as in 
later life. Its cause is supposed to be due to a deposit of 
uric acid in the fibrous structures of the naso-pharynx, 
larynx and bronchi — this deposit acting as a local irritant 
in the same manner that it does in a joint." 

One of the most freq'uent manifestations of the "rheu- 
matic" or "gouty" tendency in infancy and early child- 
hood, is eczema. Some writers call eczema a "gout of the 
skin.' Uric acid is an ^etiological factor in only a certain 
proportion of cases, however, the rest depending upon 
other diathetic conditions. 

Chorea. — Chorea is another disease of childhood 
which is now generally recognized to be of uric acid origin. 
Concerning the relationship between chorea and rheuma- 
tism, Holt, from personal observations, has noted in over 
fifty per cent, of his cases a rheumatic parentage, and 
further states : " If cases of chorea are followed for several 
years, it is surprising to note how the evidences of the rheu- 



166 URIC ACID AND ITS CONGENERS. 

matic diathesis develop the longer the cases are followed. " 
Again, Herter and Smith, who have made a study of the 
urine in chorea, found that in very many cases there was an 
excessive elimination of uric acid frequently (Holt, 721). 

Diagnosis. — In the majority of instances, it will be 
found that children, suffering from disorders due to uric 
acid accumulation, have a hard, tense pulse, some anaemia, 
and a sluggish capillary circulation accompanied by fre- 
quent excesses of urates in the urine. 

The urine is generally high-colored, scant, hyperacid 
and of high specific gravity. Frequent uric acid "explo- 
sions" occur, when the quantity of urates excreted is 
greatly in excess of the normal — three times greater in 
some cases. 

In discussing cases in which uric acid is thrown down 
in the form of crystals in the urine, or in that of the well 
known brick-dust deposit, Holt says: "This condition is 
one in which the solvent power of the urine for uric acid 
is much reduced. Such urine, as a rule, is highly colored, 
strongly acid, and may have a high specific gravity. 
This condition is dependent upon a disturbance of nutri- 
tion, and one which is most frequently associated with 
the gouty diathesis. It is not very common in children, 
except in those of gouty antecedents. " 



CHAPTER XIX. 

MENSTRUATION, GESTATION AND MENOPAUSE. 

Normal Menstruation. — It is a fact of considera- 
able interest to note, that, in the experimental study of the 
menstrual function, physiologists have discovered the 
same phenomenon that the pathologist has observed in 
connection with an attack of gout, and that is, that both 
are preceded and attended (at first) by a distinct fall in the 
output of nitrogen in urine and feces, notwithstanding 
that the amount of nitrogen ingested with the food in each 
case remains unchanged. It is further observed that, two 
or three days prior to the menstrual flow, as before the 
gout attack, there is marked retention of uric acid, as 
shown by the diminished excretion in the urine; while, 
during and immediately following the flux in both in- 
stances, the amount of urates excreted in the urine is in 
excess of normal. 

The nitrogen retention of menstruation is attributed 
by Schrader (Cf. von Noorden's Beitrage zur Lehre vom 
Stoffwechsel, II, 132) to a decreased formation of urea. 
This is doubtless true and would seem to indicate that 
at least part of the excess of urates, excreted during the 
menstrual flux, represents that portion of uric acid which 
was not oxidized into urea as normally, thus resulting in 
more of the former and less of the latter. But not all of 
this plus excretion of uric acid can be due to this cause: 
some of it, probably, represents that other and legitimate 
portion which had been previously retained, for it has been 
shown that two or three days prior to the flow, the urine 



168 URIC ACID AND ITS CONGENERS. 

contains less of the urates than normally, the excess not 
appearing until the flow is established, and continuing a 
day or two afterward. 

Two other objective signs, connected with the physi- 
ology of menstruation, are enlarged thyroidea and in~ 
creased blood pressure, both of which are doubtless caused 
by temporary demands for increased function. While the 
thyroid gland does not always appear to enlarge, yet every 
general practitioner has noticed its increase in size in 
many women at this time, only to return to its normal 
dimensions at the end of the flow. Concerning the in- 
creased demands made upon the heart, to overcome the 
effect of capillary obstruction due to the presence of urates 
in excess, Oliver {Brit. Med. Jour., I, 1375) has demon- 
strated conclusively, by means of the arteriometer, that 
there is high blood pressure in menstruation. 

Clinical Deductions. — During normal menstrua- 
tion, the retention of urates in the capillaries, just before 
and at the beginning of the flow, necessarily produces the 
customary uricacidaemic symptoms, such as depression, 
headache, loss of appetite, etc., these of course disap- 
pearing as the urates themselves disappear, as shown by 
an examination of the urine. This is what occurs each 
month, and this is all: that is, if the female is in good 
health, her organs of "defense" and excretion being equal 
to the demands made upon them for this temporary ex- 
ercise of increased function. 

But, in those cases (all too common), in which the or- 
ganism is already overburdened with uratic waste, or the 
secretions locked up from constipation or some other cause 
— the sluggish eliminative organs or those of defense being 
unable to perform their added duties promptly and satis- 



MENSTRUATION, GESTATION, ETC. 169 

factorily — then, as a result, we get classic symptoms of the 
uricacidaemic stage due to retention, ranging all the way 
from a severe headache to the most alarming neurotic 
attacks — migraine and nausea, and even violent hysteria 
or epileptiform seizures. 

The high blood pressure of menstruation will, of 
course, become aggravated under the circumstances 
mentioned above, thus indirectly tending to produce 
cardiac troubles eventually, and perhaps nutritive dis- 
turbances in the walls of the bloodvessels themselves, 
resulting in atony. 

As to the thyroid gland, it is now understood that it 
acts as an "organ of defense"; that its internal secretion 
or ferment, like those of the liver, aids in the decomposition 
or oxidation of cellular waste products (among which is 
uric acid), thus, when such waste is increased as in men- 
struation, the gland becomes temporarily congested or 
hypertrophied at the time of performing its added function. 
As this occurs regularly from month to month, it is highly 
probable that in some uricacidaemic patients, the exag- 
gerated function and consequent enlargement may grad- 
ually become greater until eventually the permanent en- 
largement results, known as Graves' disease. Probably 
the other ductless glands are temporarily congested in this 
way each month, and, perhaps, may become permanent- 
ly enlarged under similar circumstances. 

Therapeutic Conclusions. — From these clinical 
findings, deduced from the experimental study of men- 
struation, we are forced to the conclusion that to prevent 
or relieve the various disorders incident to this important 
function, the best results will be obtained by directing 
attention to the chief organs of defense and elimination — 



170 URIC ACID AND ITS CONGENERS. 

especially to liver, kidneys and bowels. Previously stored 
up uratic waste, if there be such (and there generally will 
be) , should be thoroughly removed before the expected day of 
menstruation, and in this way lighten the duties of elimi- 
nation which are known to be physiologically increased at 
this time. In short, the same rational methods should be 
employed here as have been found to be effectual in other 
similar uricacidaemic conditions. 

The reason for this physiological retention of nitrogen 
previous to and at the beginning of the flow, and of the plus 
excretion of purin nitrogen afterwards, has never yet been 
satisfactorily explained. But, as the same phenomenon has 
been noted in migraine, chorea, epilepsy, gout, and other 
uric acid explosions, we judge that it is simply one of 
Nature's laws to thus herald the approach of some 
essential strain on the part of the organism to rid itself in 
this rhythmical manner of the uratic waste products result- 
ing from sexual energy. 

"Those who have written on the subject," says Sted- 
man (Med. Rec, Oct. 7, 1905), "have agreed that the men- 
strual act exerts a well-marked influence on the various 
bodily functions, and that this depends on chemical pro- 
cesses. A stimulus which proceeds periodically from the 
genital system, gives rise to an increased metabolism, 
which in turn manifests its effects on blood pressure, 
temperature, etc. These superflous metabolic products 
are then believed to find their way back to the genital 
system, there to be eliminated until the physiological 
balance is again restored. " 

General Toxemia. — From the classic investi- 
gations of Bouchard, we know that toxic material is being 
constantly reabsorbed into the blood and eliminated from 



MENSTRUATION, GESTATION, ETC. 171 

it, consisting, in part, of that which is ingested directly 
with the food, but chiefly of the waste products of cell 
activity within the body — i. e., the precursors of urea and 
the urates. 

The organism, in health, rids itself of the toxic mater- 
ial partly by elimination and partly by chemical destruction 
or decomposition into non-toxic or less toxic substances. 
Elimination takes place chiefly by way of kidneys and 
bowels, while chemical decomposition takes place prin- 
cipally in the liver and thyroidea. It will readily be under- 
stood, therefore, that a condition of toxaemia results when- 
ever either the introduction of toxic material into the blood 
is excessive, or its elimination or chemical decomposition 
becomes insufficient. 

Toxemia of Pregnancy. — It will be seen that the 
three possible causes of the development of a toxaemic 
condition are commonly present in pregnancy, and that, 
consequently, a certain degree of toxaemia appears to be 
almost physiological for that state. First, the greater in- 
gestion of toxic material in the food is noticed in the un- 
natural longings of the pregnant woman for indigestible 
articles of diet. Second, excessive introduction into the 
blood occurs when the end products of fetal metabolism 
are resorbed into the maternal blood, which thus receives 
toxic material from both mother and fetus. Third, the 
pressure of the gravid uterus upon kidneys, liver and 
bowels, and partial compression of arteries and veins 
regulating their blood supply, may serve to interfere with 
the activity of both the organs of defense and elimination. 
In short, it must be admitted that during pregnancy, not 
only does a large amount of toxic material reach the blood, 
but the work of elimination and chemic destruction is 
hampered to some extent. 



172 URIC ACID AND ITS CONGENERS. 

It must not be forgotten that the metabolic and excre- 
tory organs of the pregnant woman are called upon to do 
extra duty: that another individual is springing into 
existence whose need for nutriment and elimination of 
waste increases with each day and hour of its growth. The 
mother must not only prepare and furnish the necessary 
building material in proper form, but she must remove the 
debris which results from the new construction. She must 
become the scavenger of, as well as serve as the outlet for, 
the child's excreta. Through the renal channel of the 
parent must be discharged the metabolites of both mother 
and fetus. In verification of this fact, we have only to 
point to the increased toxicity of the urine of the healthy 
woman during pregnancy. 

As soon as the equilibrium between importation and 
elimination of toxins is disturbed, the symptoms of auto- 
intoxication appear, and these are identical (or, atleast 
correspond closely) with those of the uricacidaemic stage 
in purin excess. They first become manifest in form of 
disturbances in the digestive and nervous system. 

Nausea and vomiting, probably the first symptoms of 
a pregnancy toxaemia, are characteristic of almost every 
form of intoxication. If the toxaemic condition becomes 
aggravated, if the patient is possibly especially susceptible 
(e. g., if uricacidaemia already exists), the vomiting may 
become very obstinate, it may develop into hyperemesis, 
into uncontrollable vomiting. There is increased reflex 
irritability, a symptom quite common for certain intoxi- 
cations in the non-pregnant state, as also after the inges- 
tion of poisons. 

Morning Sickness. — To explain the occurrence of 
toxaemic symptoms very early in pregnancy, Ehrenfest 



MENSTRUATION, GESTATION, ETC. 173 

(St. Louis Courier of Medicine, 1905, p. 200) presents a 
novel idea. "As long," he says, "as we had to regard 
fetal metabolism as the only source for toxic material, it 
seemed impossible to explain nausea or i morning 
sickness' on the ground of toxaemia. To-day, we can do 
so, because we know that just in the earliest stages of preg- 
nancy, chorionic tissue in form of the trophoblast shows a 
very marked tendency to penetrate into maternal tissue." 

In other words, this author advances the theory that 
the chorionic cover of the placenta is a most important 
source of toxic material. Inasmuch as the fetal tissue 
originates from this source, which is subsequently carried 
into the maternal system, he thinks that it is in the mater- 
nal blood that it becomes partly dissolved, causing the 
destruction of red blood cells. "In this way," says he, 
"syncytiolysins and syncytiotoxins are formed, which on 
the other hand, cause the reactive formation of the cor- 
responding antitoxic substances," — according to the Ehr- 
lich theory of immunization and its application by Veit to 
the phenomenon of deportation of fetal tissue into the 
maternal system. He believes that it is thus explained 
why we may expect to see toxaemic symptoms so early in 
pregnancy — i. e., before fetal metabolism can serve as a 
factor. 

It is evident, however, that the "morning sickness" 
may not be due entirely to this cause, that, in fact, neither 
the chorionic nor fetal tissue may be chiefly responsible; 
though, of course, there is little doubt that the symptom is 
mainly one of toxaemia. Inasmuch as it is during the first 
weeks of pregnancy that the "sickness" occurs, it would 
seem that the toxic material, which causes it, may prob- 
ably be the same as that which passes off each month with 



174 URIC ACID AND ITS CONGENERS. 

the menses, and which would have done so in this instance 
had not conception supervened and checked the menstrual 
flow. 

In other words, there is retention of the metabolic 
waste which is periodically eliminated from the genital 
system in the catamenial discharges. The physiological 
balance is temporarily interrupted; and, until the organ- 
ism succeeds in restoring this equilibrium, we observe the 
uricacidaemic symptoms (common to menstruation) thus 
aggravated during the first stage of pregnancy. 

Like the disorders of menstruation, it will be seen that 
the toxaemic symptoms of pregnancy will doubtless be 
most severe in those cases in which the eliminative organs 
are already handicapped, owing to the presence of an 
excess of urates in the circulation. That the flow through 
the capillaries is often impeded at this time in this way, 
may be seen in the almost immediate appearance of vari- 
cose veins in the lower extremities of many pregnant 
women, before the gravid uterus has become sufficiently 
enlarged to exert any pressure on the iliac veins. 

Puerperal Eclampsia. — It is obvious that the high 
toxicity of the blood during pregnancy, combined with the 
necessity of increased function on the part of the organs of 
defense and elimination, must exert a harmful effect upon 
these organs that may result in histologic alterations in 
their tissues, that under normal conditions would be con- 
sidered pathologic. Degenerative changes in the paren- 
chyma of both liver and kidneys are likely to occur; and, if 
a certain limit in such alterations be transgressed, the 
functions of these organs necessarily become interfered 
with, and toxic waste is retained. In this way a dangerous 
circulus vitiosus is formed, especially in those cases in 



MENSTRUATION, GESTATION, ETC. 175 

which the capillaries are obstructed with urates at the 
time of impregnation. 

But it is upon the liver that the work is primarily 
thrown of arresting and transforming the toxic principles 
added to the maternal circulation. This organ (aided by 
the thyroidea), during pregnancy, is engaged in a constant 
fight against a threatened toxicosis. If it fails in the 
defense, toxalbumins remain in the blood and fall upon the 
kidney whose finer structures soon become injured in the 
effort to remove the undesirable waste from the body. 
From this excess of duty, both liver and kidneys are apt to 
succumb and cease to eliminate the morbid products only 
partially. 

But, with Pinard, we believe that the kidney has only 
this secondary relation to eclampsia, and that albuminuria 
is a sign of hepatic insufficiency. In other words, we 
believe that the theory of autointoxication, which is now 
so steadily gaining ground, will ultimately be considered 
the only rational one in discussing the aetiology of eclamp- 
sia. The fact will soon be recognized that convincing 
proof has been furnished by Ehrenfest and others for 
their contention, "that nausea, morning sickness, hypere- 
mesis, or headache, albuminuria, increased patellar re- 
flexes and eclamptic convulsions, are not different dis- 
eases, but only different symptoms of various degrees of 
pregnancy toxaemia." 

It is, then, the intermediate products of nitrogenous 
metabolism chiefly — which the liver has failed to arrest 
and transform — that remain in the circulation to cause the 
autoinfection manifested by headache, vertigo, digestive 
disturbances, visual irregularities, insomnia, and various 
other uricacidaemic signs, which usually precede and 



176 URIC ACID AND ITS CONGENERS. 

usher in the "convulsive seizures." One of the great dan- 
ger signals, therefore, which may be looked for in lieu of 
albuminuria, is the absence of a normal amount of urea 
(the end product of nitrogenous metabolism) in the urine. 
For, it must be remembered that although albumin may 
be absent (which is supposed to be an indication of safety), 
yet the amount of urea eliminated may be far below nor- 
mal; in which case our prophylactic measures against 
eclampsia should at once be instituted. 

Prophylaxis. — The fact that European clinics show 
a mortality of twenty per cent, in eclampsia, would seem 
to indicate that there is still much to be desired in the way 
of rational treatment. Procrastination has always been 
the principal trouble. The perfunctory examinations of 
the urine for albumin, during the latter months of preg- 
nancy, are not sufficient. A far better plan would be to 
determine the amount of urea excreted. But even this 
is not enough; for instead of waiting until the organism 
has become sufficiently crippled to give this damaging 
evidence, it should be the aim to furnish aid that will pre- 
vent the necessity of such testimony. 

The direction which our prophylactic as well as thera- 
peutic efforts should take, may be learned from studying 
the good effects following venesection or uterine hemor- 
rhages, accompanied with enemeta of salt solution. By 
bleeding a quart, not only is considerable blood pressure 
removed, but the circulation is at once freed of twenty- 
five per cent, of its waste toxins, while the addition of the 
salt solution decreases their relative proportion. 

It mav thus be understood that the treatment of this 
condition should be eliminative. Liver, kidneys and 
bowels should be aided from the beginning. Waste should 



MENSTRUATION, GESTATION, ETC. 177 

not be permitted to accumulate until the urea or album- 
inuria sign shows the imminent danger of eclampsia. On 
the contrary, attention should be given to the first uric- 
acidaemic signs that appear — even in the first days of preg- 
nancy. 

Uricacidaemic signs, when occurring in the pregnant 
state, are much more significant than at any other time, 
and demand from the physician the exercise of his closest 
care and keenest judgment. The remedy which he has 
found to be most effectual in ridding the system of uratic 
waste in the non-pregnant state should be prescribed with- 
out hesitation at the earliest moment. Or, if the case 
should not be seen thus early, if premonitory symptoms of 
the dreaded convulsions are already manifest, even under 
these circumstances, elimination is still indicated and will 
give the best results. 

The Menopause. — The severity of the untoward 
symptoms which so often occur at the climacteric period, 
will depend in great measure upon the ability of the ex- 
cretory organs to shoulder the extra responsibility of re- 
moving from the system such waste as may still be thrown 
into the circulation periodically, and which has hitherto 
been removed to a great extent by means of the menstrual 
flow. For thirty years, or more, the organism has been 
accustomed, each month, to rid itself of certain catabolic 
products of (and by way of) the genital system, and it is 
somewhat of a shock to change all this at once. Fitful 
efforts to continue the long established function will be 
made for a time, and if the resulting waste is properly re- 
moved by way of the regular channels of excretion, no 
serious results will follow. 

But, on the other hand, if the capillaries are already 
obstructed and the circulation overcharged with uratic 



178 URIC ACID AND ITS CONGENERS. 

waste, thus rendering the organs of defense and elimina- 
tion illy prepared to perform this added duty, then the 
usual disorders, common to the uricacidaemic or rheuma- 
tic stage of purin excess, will doubtless appear. The 
toxaemic condition, in such cases, is similar in many 
respects to that of suppressed menstruation or of the. be- 
ginning of pregnancy, and the indications for eliminative 
treatment are practically the same. It will be found an 
excellent plan, therefore, to thoroughly flush out the uratic 
sewage some time prior to the anticipated period, thus 
reducing materially the work of elimination which is 
known to be physiologically increased at this time. 



CHAPTER XX. 

EYE, NOSE AND THROAT. 

Trend of Opinion. — Not only is the general prac- 
titioner beginning to recognize and appreciate the im- 
portance of eye, of nose, or of throat symptoms, when 
endeavoring to arrive at a rational diagnosis of certain 
systemic disorders, but the ophthalmologist, the rhinolo- 
gist, and the laryngologist, too, now appreciate the neces- 
sity of constitutional treatment in the management of many 
pathologic conditions found in the eye, nose or throat. 
Though, in the past, specialists were prone to attribute 
many general disturbances to the influence of the local 
disorder (which had been referred to them for treatment), 
the trend of modern opinion is to reverse this finding, and 
consider the local disorder, in many instances, as one of 
the manifestations of some constitutional dyscrasia. 

Ocular Phenomena. — The attention of the oculist 
is now being directed to the fact that many morbid con- 
ditions of the eye, which interfere with distinct vision, are 
more than mere optical disturbances : that there exists, in 
other words, an underlying constitutional dyscrasia, of 
which the eye symptoms are simply local manifestations. 

One of the first systemic disorders to be connected 
with ocular phenomena, was Bright's disease, and, today, 
the oculist as well as the physician in general practice, 
recognizes such visual disorders as "albuminuria retini- 
tis," "uremic amaurosis," "retinal apoplexy," etc., as 
indices of some unsuspected renal disease — thus serving as 
a means of early diagnosis. It has, in fact, become a com- 



180 URIC ACID AND ITS CONGENERS. 

mon practice for the specialist to refer certain eye patients 
to the general practitioner for urinalysis — provided the 
eyes of such patients fail to present apparent local cause 
for the visual disturbances complained of. 

The fact that Bright's disease is so often connected 
with uric acid retention, soon led to the discovery that 
such retention is in itself a frequent cause of optical pheno- 
mena. As early as 1890, Sanford Morton reports in the 
Ophthalmic Review, for March, of that year: "I saw 
stasis or thrombosis in the vessels of the retina, in one or 
two cases, taking place during an attack of megrim, and 
there is every probability that these troubles were due to 
uric acid." 

Prof. G. E. de Sweinitz, of the University of Penn- 
sylvania, in a paper read before the Philadelphia County 
Medical Society, November, 1902, on the subject of 
"Ocular Manifestations of Chronic Bright's Disease," 
which he considers so often a direct manifestation of uric 
acid accumulation, names such conditions as "albumin- 
uric retinitis or neuro-retinitis; alterations in the caliber 
of retinal vessels from sclerosis in chronic cases, with 
hemorrhage when general arteriosclerosis coexists; paresis 
or paralysis, chiefly of the external rectus and superior 
oblique muscles;" and especially to "recurring subcon- 
junctival hemorrhage," which latter symptom, he urges, 
has not received the attention its significance demands. 
(Cf. Tyson's " Bright's Disease and Diabetes. ") 

Iritis and Choroiditis. — The fact has for some time 
been recognized, by both the specialist and general prac- 
titioner, that congestion or inflammation of the iris is a 
frequent accompaniment of the rheumatic stage of purin 
excess, and the term "rheumatic iritis" has become quite 



EYE, NOSE AND THROAT. 181 

common in medical literature. Theobald (Reference 
Handbook of the Medical Sciences, Vol. IV) distinctly 
recognizes iritis to be of gouty and rheumatic origin. 

In a paper, read before the Fourth Annual Meeting of 
the Western Ophthalmologic Association, Feb. 10, 1899, 
Bronson treated somewhat at length the subject of "Uric 
Acid as a Factor in the Causation of Choroiditis. " "If," 
says he, "we will bear in mind the close anatomic relation- 
ship between the choroid and the iris, we will not be sur- 
prised to know that if uric acid causes a disturbance in the 
latter (rheumatic iritis), it will also in the former." Dr. 
Bronson refers to the fact that the capillary network of the 
choroid is the finest in the body and that in consequence 
of the law that the velocity of a current is inversely to its 
lumen, the velocity of the capillary current here must be 
very many times less than that of the posterior ciliary 
artery. It is well known that in the chronic toxaemias 
produced by uric acid, the earliest manifestations of necro- 
biotic changes are found in the arterioles and capillaries, 
and inasmuch as the blood current in the structure of the 
choroid is slower than elsewhere, the blood, charged with 
toxic substances, is in contact with its minute vessels 
much longer than in the larger arteries and veins. 

Temporary Visual Irregularities. — It not in- 
frequently happens to the oculist that it is almost impossi- 
ble for him to refract satisfactorily a case presenting some 
apparent anomaly of the eye, and which, perhaps, after a 
few days, or a week, can be corrected with very little 
difficulty. In some of these instances, when the patient 
presents himself, he can barely see the test chart. The eyes 
are red and irritated; lids swollen; there is strong intoler- 
ance to light, and rapid dilation and contraction of the 



182 URIC ACID AND ITS CONGENERS. 

pupil. Sometimes the eyes are bulged and staring, suffused 
with tears. 

Other uricacidaemic signs are almost invariably 
present in these cases. The urine is very scant, dark 
colored, overacid and loaded with urates. The patient 
often admits that he is just convalescing from a protracted 
alcoholic debauch. The usual alkaline eliminative treat- 
ment quickly relieves the more urgent symptoms; and, 
after a few days, no trouble will be experienced in correct- 
ing any visual irregularity, — or, the patient may now con- 
clude that glasses are not needed. 

These cases would seem to be similar to those de- 
scribed by Campbell, in his "Auto-Intoxication in Diseases 
of the Eye." After defining auto-toxaemia and a lithaemic 
condition, he says: "It has been conclusively shown that 
almost, or quite all the tissues of the body suffer inflam- 
matory reaction in the event of auto-intoxication by the 
cellular waste products above indicated. The various 
effects upon the lids, upon the conjunctiva and cornea, 
have been gone over again and again/' 

Astigmatism. — In the International Clinics (Jan., 
1900), Vol. IV, p. 173, in an article entitled "A Few 
Thoughts Indicating a Causative Connection Between the 
Uric Acid Diathesis and Astigmatism," Louis J. Lauten- 
bach, M. D., Ph.D. (Surgeon in charge of the Phila- 
delphia Eye, Nose and Throat Institute), states that for 
several years he has been suspicious that the phenomena 
attendant upon cases in which astigmatism was present, 
were in some way connected with an increase in the quan- 
tity of uric acid retained in the system; and it is only 
recently that the conviction forced itself upon him that the 
connection is too constant to be accidental, and that some 



EYE, NOSE AND THROAT. 183 

causative relation must exist between the two conditions. 
Of forty-two cases of astigmatism examined by him, uri- 
nalysis revealed in every instance, urine typical of the 
lithaemic condition, — being overacid, of high specific 
gravity, developing an excess of uric acid elements. After 
the employment of the alkaline eliminative treatment in 
these cases, assisted by the use of proper glasses, the astig- 
matism invariably disappeared. Uratic deposits in con- 
junctivae and skin also disappeared, the latter organ be- 
coming softer and moister, losing that dry, scaly appear- 
ance and the itching so characteristic of the uric acid 
dyscrasia. 

Nasal Affections. — It is now quite generally agreed 
upon by rhinologists that polypoid degeneration of the 
ethmoidal bodies, in part or in whole, is in many cases the 
result of repeated uric acid irritation of these bodies. 
Study of certain cases, supplemented by extended obser- 
vation in a number of others, makes clear what might be 
expected — removal of nasal polypi no more cures asthma 
than would the removal of tophi about the joints of the 
fingers cure gout. Results have proven, in both cases, that 
the anti-uric regime is most effective. 

Freudenthal describes a condition of inflammation of 
the turbinates, in connection with rheumatic arthritis else- 
where; and reports several cases, a number of which he has 
seen. He thinks many cases of what are called simple 
"coryza" may be rheumatic, and sees no reason why the 
nose should not be affected, even though the articulations 
there do not happen to be as typical as those in other parts 
of the body. 

Hay Fever. — Although other theories have been 
suggested from time to time, but one can be said to have 



184 URIC ACID AND ITS CONGENERS. 

stood the test of clinical experience; and, today, there is a 
general consensus of opinion among the best informed, 
that the following are the essential ^etiological factors in the 
production of hay fever; to wit: I. An external irritant. 
2. A sensitive local surface, due (a) to uric acid ob- 
struction, or (b) to anatomical abnormalities of the naso- 
pharynx. 

That something besides an "external irritant" is neces- 
sary to produce this complaint is evidenced from the immu- 
nity enjoyed by country people, who are, as one writer sug- 
gests, "surrounded by a pollen-laden atmosphere during 
the whole period of vegetation, while the dust in the roads 
is often several inches deep during the dry weather of the 
summer, and passing teams raise clouds of dust that float 
in the air for several minutes. The natives of these rural 
localities are not free from the irritant pollens that cause 
hay fever in city dwellers, for the ever present ragweed 
grows in luxuriance, and the golden rod blooms by every 
roadside and their pollens float on every breeze." 

The fact that victims of hay fever are found among 
those of sedentary habits; among professional and busi- 
ness men of the populous centers, with whom ingestion 
of food is out of proportion to physical exercise; among 
the inhabitants of cities who indulge most freely in the 
meats and sweets of the table; and especially among the 
"gouty" inclined, — is a strong indication of its autotoxic 
or purin origin. 

It is a well-known fact, too, that hay fever never oc- 
curs in an individual with perfectly healthy nasal passages; 
the capillaries of the latter being obstructed, turgescence 
of the mucous membrane, with frequent swelling of the 
tissues, is an inevitable consequence, and a sensitive sur- 



EYE, NOSE AND THROAT. 185 

face is exposed to the external irritant. The important 
function of the nasal mucosae of purifying the inspired air 
and neutralizing countless germs, is illy performed; and 
doubtless, ptomaines from the decomposed secretion not 
only serve as a local poison, but may enter the general 
circulation. Other uricacidaemic or rheumatic signs are 
commonly present; while the urine is concentrated, heavy, 
and loaded with lithates. 

The clinical picture is typical of uric acid excess, with 
obstruction of the nasal capillaries; and the results ob- 
tained from the alkaline eliminative treatment have thus 
far proven most satisfactory. 

Concerning the nature and cause of the suddenness 
of the attack or paroxysm, in many cases, Bishop (Dis- 
eases of Nose, Throat and Ear, p. 39) offers the following 
explanation: u As a tumor or hypertrophied bone may 
give rise to convulsive seizures in epilepsy, and as its re- 
moval may be followed by relief when no other structural 
cause exists, so in hay fever, where new growths and other 
lesions of the nasal mucous membrane are present, the 
attack may be started by the accumulation and the sud- 
denly setting free of uric acid. This precipitates the par- 
oxysm by its irritant action, which finds expression in the 
group of symptoms characteristic of nervous catarrh or 
asthma, instead of one of the other allied diseases. The 
particular form of manifestation may be determined by 
the growth or seat of irritation, located in the nasal cavi- 
ties. Where this is the only determining factor of the 
nature of the morbid symptoms (no other organic disease 
having resulted from the long-standing trouble) the re- 
moval of such a peripheral source of irritation may give 
relief from these symptoms, but it may not prevent the 



186 URIC ACID AND ITS CONGENERS. 

uricacidaemia from switching of? into other kindred lines 
of disturbances, if not corrected. The uric acid theory 
makes clear the reasons why some persons suffer from at- 
tacks of nervous coryza under certain favorable conditions 
in winter as well as in summer months. It also unifies all 
the various forms of hay fever. " 

Lith^mic Sore Throat. — The resemblance of the 
nasal mucosae of hay fever sufferers to the "lithaemic sore 
throat," described by Sir Morell MacKenzie (Journal of 
Laryngology and Rhinology, Vol. Ill, No. 8), is suffi- 
ciently striking to augur a similar causation. 

"The lithaemic throat," says this eminent author, 
"is usually uniformly red, the tonsils are slightly swollen, 
the uvula elongated and thickened, and all these parts 
bathed with a considerable amount of mucous secretions. 
The urine is heavy, small in quantity and loaded with 
urates. One peculiarity of the lithaemic throat," says he, 
(and this is also true of the nasal passages in hay fever), 
"is the fact that the applications of a stimulant or an as- 
tringent nature, instead of affording relief to the patient 
are apt to cause additional distress." MacKenzie's 
theory of the causation of the underlying constitutional 
trouble, is that of subalkalescence of the blood and sub- 
oxidation — uric acid and its congeners being the chief 
resultant products. 

Frequent attacks of tonsillitis (the so-called rheu- 
matic tonsillitis), alternating with the customary uricaci- 
daemic or rheumatic signs of purin excess, is a very com- 
mon indication of the lithaemic throat. 

Therapy. — The character of the general treatment, 
in these stubborn complaints, differs in no wise from that 
which is indicated in other uricacidaemic or rheumatic 



EYE, NOSE AND THROAT. 187 

conditions. "The irritable throat of lithaemia," Mao 
Kenzie states, "is sometimes amenable to abstention 
from wine and too much nitrogenous food, with the ad- 
ditional aid of a brisk purgative." 

For the relief of lithaemic affections of the skin and 
mucous membranes, Piffard mentions one or two objects 
which should constantly be kept in view. i. The depur- 
ation of the blood. 2. The increased oxidation of ali- 
mentary substances. "The first object should be attained," 
he says, "by the use of alkaline diuretics, by laxatives, and 
by increasing elimination by way of the skin." The 
second object is attained "by stimulating the action of 
the liver and increasing metabolism." In short, the alka- 
line eliminative treatment is indicated here, as elsewhere. 



CHAPTER XXL 

TRAUMATISMS AND SURGICAL NOTES. 

Joint Injuries. — The cause of the protracted and 
painful convalescence, often following some trifling in- 
jury to the joint, has of late been a subject of fruitful dis- 
cussion among many eminent clinicians and surgeons. 
The unsatisfactory outcome of a purely local treatment, 
in the handling of certain cases of lame and partially 
stiffened joints, due originally to strain or injury, has led 
to the belief that some underlying constitutional factor 
must be held responsible. 

After a careful study of the question from a clinical 
standpoint, watching results from different lines of treat- 
ment in an extensive series of cases, Prof. William H. 
Porter, of New York, in an article, "To What Extent 
Does Rheumatic and Gouty Diathesis Enter into Trau- 
matic Joints, i. e., Sprains and Bruises ?" read before the 
Massachusetts Medical Society, at Boston, June 13, 1900 
(Cf. Medical Record, Sept. 22, 1900), has this to say: 
"The relationship of the so-called gouty and rheumatic 
condition of the system should always be taken into con- 
sideration in connection with every traumatism that impli- 
cates the joints. If such a state of the system is found 
to be present, it must be given due consideration in the 
general management of the case; otherwise, recovery 
will be greatly retarded/' 

Practically the same conclusion was arrived at by the 
late Prof. Thomas H. Manley, of New York. In a paper 
on the "Constitutional Treatment in Joint Injuries" (Cf. 



TRAUMATISMS AND SURGICAL NOTES. 189 

New York Lancet, Jan., 1901), he states: "When there- 
fore, we meet with severe arthritis after joint injury, and 
this fails to respond to ordinary therapeutic measures, we 
should carefully investigate into the environment of the 
patient, his habits, his antecedent history, and examine 
well into his general condition. The most common com- 
plication is rheumatic. We must resort to the therapeutic 
test; in other words, treat the patient as well as his injury. 
In order to reach the system, and eradicate the cause, 
when rheumatism is present, internal medicine should be 
simultaneously given in all cases." 

Similar advice is given by the late Prof. A. M. Phelps, 
of New York. In considering the subject of hip-joint 
disease, he refers particularly to the rheumatic joint, pre- 
ceded by an injury, in which cases constitutional treat- 
ment is always required in addition to the mechanical 
and operative. {Peoria Medical Journal, Dec, 1898.) 

A good illustration of the value of such advice, in the 
class of traumatisms under discussion, is seen in a brief 
published report of the experience of Dr. W. T. Tilney, of 
Crawfordsville, Ind., which will doubtless recall to the 
minds of many physicians similar cases that have been 
met with in their practice. The doctor states that he 
suffered for two years with a stiff-knee joint, which he had 
sprained. All local treatments had failed, and he had about 
given up hope of getting any relief. It finally occurred to 
him that the trouble might be rheumatic, and he at once 
instituted the alkaline eliminative treatment with success- 
ful results. In a short time the lameness entirely dis- 
appeared; and six months afterwards (Sept. 20, 1901) 
he reports that the joint still remained in its normal 
condition. 



190 URIC ACID AND ITS CONGENERS. 

Another similar case, though one more serious and 
of much longer duration, is reported by Smith, in the St. 
Louis Medical and Surgical "Journal, March, 1901. In this 
case, the doctor suffered for six years, before instituting 
the proper treatment. His trouble, also, was in the knee- 
joint, — i. e., synovitis, following an injury, which confined 
him to the house for several weeks, and from which he 
recovered with permanent slight stiffness. Three years 
afterwards, the knee began to enlarge, gradually increas- 
ing in size until nearly twice as large as normal. He was 
forced to give up his work, and for three months sat in a 
wheeled chair. He went into a sanitarium and was 
treated with baths, electricity, massage, etc., but with 
little benefit. He remained in this unsatisfactory and prac- 
tically helpless state, until the summer of 1899 — nearly 
three years. At this time — other joints having, in the 
meantime, become somewhat affected, and noting urate 
deposits in quantity in the urine — he began the alkaline 
eliminative treatment for rheumatism. In a few days, the 
joint began to decrease in size and the general health to 
improve. In September of that year, after a short visit to 
the Catskills (where he had continued treatment), the 
doctor returned home and re-entered into practice. Eigh- 
teen months afterward (March, 1901) he reports that he 
is a "new man;" that, with the exception of occasional 
"slight stiffness" of the knee, he is as well as ever, weighing 
within five pounds as much as he did before the attack. 

The Interpretation. — Judging from the symptoms 
and clinical history of many cases, it would seem that, 
though a swollen and inflamed joint may be traced to an 
injury and apparently be entirely due to the latter, never- 
theless deposits of urates may immediately center at that 



TRAUMATISMS AND SURGICAL NOTES. 191 

point and serve as a further source of irritation and hind- 
rance to natural recovery. Especially is this likely to be 
true, if the patient chance to be suffering already from an 
excess of urates in the circulation at the time of the injury. 

Owing to the local congestion following upon a trau- 
matism of the joint, the urates as well as leucocytes are 
brought to this point in increased quantity; and, as the 
surrounding lymph and synovia become reduced in alka- 
linity, the conditions are favorable for the precipitation 
of the urates, which become attached to the contiguous 
solid fibrous tissues. 

The urate salts have a well-marked tendency to seek 
out the fibro-serous structures (or white tissues) con- 
nected with the locomotor apparatus — those subject to 
strain; and, as acid is produced as a result of contraction, 
precipitation occurs at this point and becomes a nidus or 
center for the attraction of further deposits. The mechani- 
cal or chemical irritation, resulting from the presence of 
these crystals, may usher in an attack of arthritis resem- 
bling that of acute gout. 

It will be readily understood that, until the removal 
of such deposits, either through phagocytic action or the 
return of the blood's alkalescence normally produced, or 
through increased solvency of the blood produced medi- 
cinally, the case is likely to prove stubborn and conval- 
escence protracted. 

Other Traumatisms. — Of the various other joint 
lesions, in which may develop severe and harassing rheu- 
matoid pains, may be mentioned those following contu- 
sions, fractures and dislocations. Indeed, the after pains, 
in many cases, are even more troublesome than the original 
injury, which they usually follow within a fortnight or a 



192 URIC ACID AND ITS CONGENERS. 

month. In some cases, the subsequent pain is out of all 
proportion to the injury; it lasts a long time and is rebel- 
lious to local treatment. As to internal treatment, the 
same advice is offered here as in that of sprains, and the 
resultant swelling and stiffness, already considered. The 
same explanation is also given as to the cause. 

Sluggish Ulcers. — Abrasions or contusions of the 
surface of the lower extremity, especially in the tibial 
region where the circulation is naturally sluggish, may de- 
velop into unhealthy sores or varicose ulcers, which resist 
all local forms of treatment. This untoward result is 
more likely to happen if the capillaries in that vicinity are 
obstructed with urates (as shown by cramps and cold 
feet), thus preventing a free flow to the injured surface 
and growth of healthy granulations. 

In these cases, in conjunction with the local methods 
usually employed, the alkaline eliminative treatment is 
indicated as in the joint injuries previously described, and 
for the same reason. If uricacidaemic signs already exist, 
or have previously existed, no further doubt is to be enter- 
tained that the sluggish action of the part is due to ob- 
struction of the circulation from urates; and the proper 
measures should be taken accordingly. 

A Surgical Hint. — In a recently published article 
in the International Medical Magazine, Montgomery 
(Professor of Gynecology, Jefferson Medical College) has 
voiced the sentiment of the great body of modern surgical 
operators, in the statement that the highest success in sur- 
gical procedures is attained when all factors, which are 
likely to disturb the subsequent convalescence, are, so far 
as possible, recognized and eliminated. He believes that 
in surgical operations, the eliminating powers of the 



TRAUMATISMS AND SURGICAL NOTES. 193 

patient should be restored to their most effective condi- 
tion, and that any condition which is likely to clog the 
metabolic processes or those of oxidation, should be cor- 
rected. He says that one of the most important disturb- 
ances of this function, whose baneful influences are too 
frequently underestimated, is uricacidaemia; that patients 
affected with this condition do not bear surgical operations 
well. The convalescence is complicated by defective 
elimination through the kidneys, etc. The lessened re- 
sistance induced by uratic obstruction favors the occur- 
rence of localized congestions and inflammations, which 
may frequently be the cause which favors the develop- 
ment of sepsis. 

"Every operator," says Montgomery, "has witnessed 
the development of untoward manifestations where the 
slight extent of the operation, the apparent good health 
of the patient, and the scrupulous care exercised during 
operation, justified him in anticipating the most favorable 
results. A careful scrutiny in many cases demonstrates 
the uric acid condition under consideration to have been the 
factor which has turned the scale in the wrong direction. " 

The fact is becoming better recognized every day that 
it is particularly important to establish a normal function- 
ating activity of the liver, kidneys and bowels, prior to 
surgical procedures; for, if the excretory organs be inac- 
tive or impaired from any cause, the normal reparative ener- 
gies of the body will become so weakened after an operation 
that recovery is doubtful. Not only is it considered neces- 
sary to examine the urine for evidences of casts, sugar 
or albumin, but for the presence of an excess of urates, 
or of lack of urea. 

A Determining Factor. — The fact that the victim 
of purin excess, whether in the uricacidaemic or rheumatic 



194 URIC ACID AND ITS CONGENERS. 

stage, is notoriously deficient in excretory powers, has 
led to the conviction that among the determining factors 
which prevent proper recovery from surgical operations, 
by choking the capillaries and impeding normal repara- 
tive processes, must be reckoned the purin or ureid bodies, 
of which uric acid is the type and chief representative. It 
is doubtful if any other of the metabolic waste products 
are so commonly retained and produce so much trouble, 
by interfering with the processes of nutrition and' elimina- 
tion, as does this retrograde cellular tissue product under 
discussion. 

It was the generally accepted belief among the mem- 
bers of the profession, that had President McKinley (at 
the time of the wound and operation which proved so 
disastrous) been in the prime and vigor of health, with 
organs of secretion and excretion equal to the full per- 
formance of their duty, the wound and operation might 
not have proven fatal. It is believed that the impairment 
of the metabolic functions and gradual accumulation of 
toxic waste products within the system served to paralyze 
reparative energy when the occasion demanded. The 
necessity of immediate operation rendered it impossible 
in this instance to rid the organism of purin waste in the 
manner recommended in such cases. 

The local irritation of tissue observed in the diabetic 
patient, when injured or operated upon, is well known to 
the surgeon. The frequent association of gout and dia- 
betes has caused much speculation as to the probable 
similarity of origin of these two complaints — though one 
represents faulty metabolism of nitrogenous products and 
the other of the carbo-hydrates; and much food for reflec- 
tion is afforded the thoughtful physician in such cases as 



TRAUMATISMS AND SURGICAL NOTES. 195 

that of the lamented McKinley. Was he suffering from 
purin excess (or the so-called "gouty diathesis"), and were 
retrograde tissue products present in such quantity as to 
serve as a disturbing factor ? 

We know that when the normal interchange between 
blood and tissue is interrupted, the latter dies for lack of 
nutriment. We know that gangrene, or death of cells, is 
the result of nutritive failure, i. e., either no nutriment is 
brought to the cell (capillary circulation being obstructed) 
or else the toxic waste products of cell disintegration are 
allowed to accumulate and choke absorption — and the cell 
languishes in the midst of its own excreta. The necessity 
of freeing the capillaries of such obstruction, before an 
important surgical operation, at once becomes manifest; 
and it is largely for this purpose that eliminative remedies 
are now recommended as a precautionary measure to such 
procedures. 

It is now becoming better understood and appre- 
ciated that anything which interferes with the functional 
activity of the excretory organs and prevents the free 
elimination of cellular waste, not only causes the blood to 
become loaded with deleterious matter that renders it less 
able to take up the further retrograde products of cell 
activity, but that the blood (thus overloaded) less readily 
conveys the nutrient material which is absolutely necessary 
to the life and health of the cells; and, furthermore, the 
accumulating toxins not only inhibit the activity of the 
cells, but lessen their power to recognize and combat mal- 
eficent agents. We begin to realize to how great an ex- 
tent the welfare of the body depends on the consentaneous 
activity of the cells, the blood and the excretory organs; 
and, also, to appreciate the importance of autointoxica- 



196 URIC ACID AND ITS CONGENERS. 

tion as an important factor in the production of a dis- 
turbed condition unfavorable to the growth and repair of 
tissue — always so essential after surgical operation. 

In short, the patient operated upon (with unsatis- 
factory results) may have suffered no infectious nor con- 
tagious disorder; he may not have been exposed to an en- 
vironment which his system was unable to cope with — 
i. e., he may have had no poison introduced into his body 
from without; he had simply neglected to rid himself of 
the poisons generated within. An important point, then, 
to be observed before operation, is to devote (whenever 
possible) a few days to the preparation of the patient — 
i. e., shake down the grate and clean out the ashes and 
clinkers: remove the slag. Prof. Augustin H. Goelet, of 
New York, in discussing this subject of preparation of the 
patient, especially for abdominal operations, recommends 
that from one to three weeks, at least, should be consumed 
in getting the patient in condition. He gives careful atten- 
tion to the diet, and prescribes such eliminative agents as 
will best stimulate the action of the kidneys, liver and 
bowels. He believes that the alkaline eliminative treat- 
ment, employed in this way as a preparatory measure, will 
enable the surgeon to do "better work in a shorter time 
and will materially lessen the mortality following abdom- 
inal operations." (Cf. Charlotte Medical Journal, Dec, 
1898.) 



CHAPTER XXII. 

SOME USUALLY UNRECOGNIZED URIC ACID CONDITIONS. 

Spine and Lower Extremities. — In a paper en- 
titled "Manifestations of Lithaemia in the Spine and 
Lower Extremities, Simulating Orthopedic Conditions," 
read at the meeting of the Buffalo Academy of Medicine, 
May 2, 1905 (Cf. American Medicine, Sept. 30, 1905), 
Le Breton calls attention to a class of cases not described 
as such in text books. He excited no little interest in re- 
porting a series of nine of these cases, which had been re- 
ferred to him by general practitioners in different portions 
of the state during the past two years, for orthopedic treat- 
ment; but in which such treatment was shown by him to 
be of minor importance, as compared with the constitu- 
tional measures he employed to eliminate from the system 
the true aetiological factor, and thus relieve the underlying 
condition — the so-called "lithaemia," "irregular gout," 
"a rheumatic tendency," etc.; or, as he says: "A condi- 
tion in which nutrition is at fault, oxidation imperfect, and 
organs functionally deranged." 

Symptoms. — Of the nine cases reported by Le Breton, 
eight were females ranging in age from twenty to thirty. 
The chief symptom always complained of, was either 
backache or pain in the feet, of such a character as to lead 
to the diagnosis of flat-foot or of some spinal condition 
requiring support. 

Questioning usually elicited acknowledgement of the 
following symptoms: — Indigestion, with excess of gas; 
pain after eating, and sour eructations; constipation; a 



198 URIC ACID AND ITS CONGENERS. 

general lack of energy and of strength; a tendency to dizzi- 
ness, fainting and cardiac palpitation; general nervous- 
ness, insomnia and paresthesias. Goitre occasionally 
present. 

Urinalysis usually revealed a hyperacid urine, of high 
specific gravity, the quantity being less than a quart in 
twenty-four hours. Or, again, less frequently, it might be 
alkaline, of low specific gravity, the quantity being abnor- 
mally high for the twenty-four hours. Rarely is a normal 
urine found. 

"When backache is the major symptom, it is apt to 
be localized between the shoulders or in the lumbar region. 
Two or three spinous processes are found to be tender on 
pressure. The ribs and surrounding muscles are often 
sore to the touch. Tender points are sometimes dis- 
covered over various peripheral nerves, especially the 
sciatic nerves. Motions of the spinal column may cause 
pain. When motion produces pain, an advantageous ad- 
junct in the treatment is to have the patient wear for a few 
months a light jacket. 

When pain in the feet is the chief complaint, the site 
of the pain may be widespread, as, for example, through- 
out both feet and in both calves; or it may be localized in 
the ball of the foot, or in the heel, or some particular tarsal 
joint. Pressure reveals deep tenderness in the ball of the 
foot, or over the plantar fascia, or dorsum of the foot. 
Pressure over the sciatic nerves very often finds typic 
tender points over both nerves and over the roots of these 
nerves in the lower part of the back. Occasionally wide- 
spread tenderness is present over all the muscular tissues 
of the lower extremities. It is a noticeable fact that until 
these patients have had general treatment, they are utterly 



UNRECOGNIZED URIC ACID CONDITIONS. 199 

unable to endure the pressure of plates or a lift in the shoes, 
even if there is a flat-foot." 

Therapeusis. — "The curative treatment," says Le 
Breton, "is one directed at the diathesis; for support 
by jacket or flat-foot plate may be only secondarily indi- 
cated." In every instance, successful results were ob- 
tained by ordering regular hours, proper exercise and diet, 
plenty of water, and an alkaline eliminant remedy. Im- 
provement is usually manifest at once, unless the neuras- 
thenic element is strongly developed. In some instances, 
local treatment may consist of static electricity, massage 
or the mechanical vibrator. Later, Blaud's pills and 
general tonics may be indicated. 

Precaution. — Ordinarily, these well-known signs 
of uricacidaemic or rheumatic stages of purin excess are 
easily recognized and the proper treatment instituted; 
but, in the class of cases under discussion, the underlying 
condition is so masked by one or the other of the two 
prominent symptoms mentioned, that a wrong diagnosis 
is apt to be made. A complete cure, however, may usually 
be looked for, if the true condition is recognized and the 
proper alkaline eliminant treatment employed. It is evi- 
dent that the urates in these cases are deposited chiefly in 
the neighborhood of the rigid articulations of the spine and 
tarsus, rather than in the more flexible joints and muscles 
at other portions of the body, as is commonly the case. 
For this reason, the pains in the back and feet overshadow 
the other general symptoms, which differ in no wise from 
the usual uricacidaemic or rheumatic signs. 

Growing Pains. — Another conspicuous symptom 
of purin excess, the true nature of which is generally 
unrecognized or overlooked, is that manifestation of the 



200 URIC ACID AND ITS CONGENERS. 

rheumatic stage popularly known as "growing pains. " 
The rational treatment indicated in these cases is often 
withheld by the physician, owing to the mistaken idea that 
nothing abnormal exists, that the pains are simply evidence 
of the rapid growth of a healthy physical organism. 
Though pediatrists have frequently called attention to the 
rheumatic character of the symptoms, the popular fallacy 
has become so firmly rooted that little heed is given to 
such warnings. 

Sixteen years ago, in his Therapeutics of Infancy and 
Childhood (Cf. Archives of Pediatrics VI, 6, p. 355), Jacobi 
sounded a note of warning on the subject, in the following 
significant paragraph: "The large majority of attacks 
of 'growing pains,'" says he, "means rheumatism; it is 
the failure to appreciate this fact that gives rise con- 
stantly to mistakes in diagnosis, and the neglect in the 
administration of both preventive and curative measures. " 

Again, more recently, in a magazine article, (N. T. 
Med. Jour, and Phila. Med. Jour.. Sept. 30, 1905), 
Satterlee, in concluding his discussion of "Rheumatic 
Poison and Its Treatment," has this brief admonition to 
offer: "In closing, I would earnestly call attention to the 
importance of recognizing and treating all rheumatic con- 
ditions in children, like the so-called 'growing pains' and 
frequent attacks of follicular amygdalitis, etc., especially 
where they have an hereditary history of any of the diseases 
of rheumatic poison in parents or grandparents." 

Another notice, given along these same lines, is that 
of Barbour (Amer. Practitioner and News, March, 1905) 
in "Some English Views on Rheumatism," in which he 
says: "In England, as well as here, the fact that rheuma- 
tism is more frequent and more serious in childhood than in 



UNRECOGNIZED URIC ACID CONDITIONS. 201 

adult life is not appreciated, and authors of text-books 
still write fatuously of its frequency in early adult life, and 
of its rarity in children. Such errors die hard, and, un- 
fortunately, carry in their train numberless mistakes in 
diagnosis, and unnumbered pains, illnesses and deaths. 
Until the profession at large recognizes that 'growing pains' 
are rheumatic in origin and a frequent cause of organic 
heart lesions, the work of education must be kept up." 

'The English pediatricians," continues this author, 
''are doing yeoman service in arousing trie profession to a 
knowledge of all the varied manifestations of rheumatism 
and to an appreciation of its importance. As one of the 
most eminent of their pediatrists said to me: 'Twenty- 
five per cent, of all cases in the children's hospitals suffer 
from rheumatism in one form or another.' The large in- 
cidence of rheumatism in London would seem to follow 
on the excessive dampness and the overcrowding; and the 
older men still recognize the importance of these factors, 
as predisposing causes, probably by lowering the resist- 
ing power of the organism." 

^Etiology. — -As referred to in the foregoing remarks, 
"dampness and overcrowding" may probably serve to 
some extent as predisposing factors, in the aetiology of the 
rheumatic condition in London children; to which, we 
may add, that dampness and cold serve also as exciting 
causes, not only in London but in America. "Growing 
pains," muscular pains, etc., must all be grouped together 
as characteristic signs of the rheumatic stage of purin ex- 
cess, all of which are indicative of the deposition of 
urates chiefly in the white tissues (sheathes of muscles, 
aponeuroses, bursas, capsular ligaments, pericardium, en- 
docardium, or in the joints) : such deposits often being pre- 



202 URIC ACID AND ITS CONGENERS. 

cipitated through reduced alkalinity of the lymph or blood, 
caused by the exposure of the surface vessels to cold and 
dampness — especially after violent exercise. 

The apparent greater liability of boys and girls ap- 
proaching puberty, to these transient deposits, thus giving 
rise to "growing pains," is probably due in considerable 
measure to the suddenly increased cellular metabolism of 
the genital system, incidental to the transformation of the 
hitherto latent sexual energy into functional activity, and 
the consequent necessity of increased elimination of purin 
waste. The exposure of the body to inclement weather at 
this time, serves as an exciting factor to cause deposition 
of urates, even though the latter be but little in excess of 
the normal. The rheumatic signs produced will usually 
be temporary in these cases, owing to the activity of the 
excretory organs and abundant oxygen supply in the 
youthful organism. The danger, however, of the deposi- 
tion occurring in the endo- or pericardial tissues, should 
urge the adoption of preventive or curative measures in 
the way of alkaline treatment, precisely of the same char- 
acter as that recommended in the rheumatic stage of purin 
excess in the adult cases. 

Raynaud's Disease. — This disorder, commonly 
discussed under the head of "symmetrical gangrene," was 
first described by Raynaud, in 1862; who found that it 
occurred most frequently in convalescence from exhaust- 
ing illness, and in chlorotic, nervous individuals in early 
adult life. The disease is usually described in text-books 
as "a neurosis characterized by an exaggeration of the 
excito-motor power of the cord in presiding over the vaso- 
motor centers, as shown by vascular spasm, venous or 
arterial, in symmetrical parts of the body." 



UNRECOGNIZED URIC ACID CONDITIONS. 203 

In his "Thesis" (p. 166), Raynaud says: "The ex- 
tremities are most often affected because these are the por- 
tions of the body which have most surface in proportion 
to bulk, and therefore most likely to lose their heat by con- 
duction and radiation, and most early become cooled down 
below the point at which the life of the tissues can be con- 
tinued." 

The foregoing is significant in showing what great 
importance Raynaud attached to the causative influence 
of exposure to cold. 

Local Signs. — The phalanges are the parts most 
commonly affected, especially of the fingers; also the tip 
of the nose and external ear. At first, the surface is cold, 
white and bloodless (without feeling dead) ; the skin be- 
comes wrinkled and shrunken; the ends of the fingers, 
thin and conical. Afterward, there is itching and severe 
pain, followed by a bluish skin and finally gangrene. 

The local asphyxia may be partial, producing merely 
a temporary ischaemia, cyanosis, or erythema, in which 
case there is likely to be frequent recurrences of the trouble, 
or the asphyxia may be so complete and continued as to 
produce absolute gangrene. Treatment has usually been 
of no avail. 

The Uric Actd Theory.— Haig was the first to 
point out the probable uric acid origin of this affection; 
having been led to the discovery by the slowness of capil- 
lary reflux on the surface of the extremities (observed after 
slight digital pressure), in all cases of uric acid excess in the 
circulation. He at once concluded that the aspyhxia of 
the part in Raynaud's disease might be caused bv uric 
acid collaemia, which he defines as a condition of obstruc- 
tion in the capillaries through a thickened or viscid state 



204 URIC ACID AND ITS CONGENERS. 

of blood, producing stasis, subnutrition, and finally gan 
grene. This stasis in the surfaces, especially at the ex- 
tremities, as he very properly avers, will be still further 
hastened by the action of cold. 

In support of Haig's theory, Rosewater recently pre- 
sented the report of "A Case of Lithaemic Gangrene,'' in a 
paper read before the Clinical and Pathological Section of 
the Academy of Medicine, Cleveland, Ohio, 1905, and 
demonstrates very clearly that the so-called Raynaud's 
disease, from which his patient was said to be suffering, 
was simply one of a series of symptoms due to uric acid 
toxaemia, which yielded readily enough to the proper die- 
tetic and medicinal treatment. The following is a brief 
summary of the case; to wit: 

"A man, sixty-four years old, emphysematous, rheu- 
matic for thirty-five years (for the past eight years suffer- 
ing with asthma and bronchitis) with a history of previous 
superficial gangrene, is treated for gangrene of the anterior 
right tibial surface by elevation, antisepsis, heat, andalac- 
tocereal diet. Discharged cured in six weeks. Advised to 
continue the diet (antilithaemic) and soon reports that his 
asthmatic difficulty is decidedly relieved; six weeks later, 
while on this diet, but three hours after eating a beefsteak, 
a violent pruritus develops. Relief and cure follow return 
to the lactocereal diet; but after two months, he develops, 
February, 1902, a superficial gangrene of all toes but the 
third of the right foot. He had observed the diet, except 
that for fully one month he had twice daily a cup of beef 
tea. The flesh sloughed off, but reformed on the indicated 
treatment and diet. 

Seven months later, he complains of loss of memory 
and mental unbalance. His diet was kept up, except that 



UNRECOGNIZED URIC ACID CONDITIONS. 205 

he was daily drinking tea and coffee. On strict observance 
of the diet, he has remained well now for over seventeen 
months. 

The history of this case : lithaemic stigmata, deviation 
from normal each time uric acid or purin food was added 
(each time only one incriminating article), and the patient's 
return to and maintenance of normal health, when strictlv 
on the diet, is as diagnostic of lithaemia and as justifiable, 
as would be potassium iodide and mercury for lues. 

The gangrene was superficial and accompanied by a 
relative stasis of the blood stream, and not by a toxic con- 
traction of arterioles; due likely, as Haig states, to uric 
acid viscosity, as apparently corroborated bv Romberg, 
who found that the blood stream might vary fully ten per 
cent, in viscosity, which, in arteriosclerosis and other con- 
ditions, must be extremely injurious, especially in the cap- 
illaries and to the heart." 

Conclusion. — The case reported by Rosewater, 
together with several others cited by Haig, fairly demon- 
strates the fact that occlusion of the capillaries (generally 
at the venous end) by urates, may prevent the return flow 
of blood from the poorly vascularized extremities, and 
give rise to the production of the same series of objective 
symptoms, as would follow from a ligature of the part. 
The normal interchange between blood and tissue cell is 
interrupted; and, if the obstruction is complete and per- 
mitted to remain long enough, the cell languishes and 
dies in the midst of its own excreta — i. e., gangrene results. 
But, if the obstruction is only partial, we get the usual 
signs of temporary ischaemia, cyanosis, erythema, etc. 

The fact that other uricacidaemic signs are invariably 
present; that ingestion of purin foods and drinks speedily 



206 URIC ACID AND ITS CONGENERS. 

aggravates the local condition; and that withholding 
further introduction into the system of such foods and 
drinks, taken in conjunction with the employment of anti- 
uric-acid treatment affords speedy relief, — would seem to 
furnish satisfactory clinical evidence of the uratic origin 
of this affection. Indeed, from a theoretical viewpoint as 
well, the established physico-chemical facts are sufficiently 
abundant to warrant the classification of Raynaud's dis- 
ease among "some usually unrecognized uric acid con- 
ditions. " 



CHAPTER XXIII. 

DENTAL CONDITIONS. 

The Teeth. — The three anatomical divisions of the 
tooth, with which, from a uric acid standpoint, we are 
particularly interested, are (i) the peridental membrane, 
(2) the tooth-pulp, and (3) the dentine. The surrounding 
alveolar tissue and gums are usually affected secondarily. 

The peridental membrane, which envelopes the root 
of the tooth, in its alveolar socket, may be considered in 
the light of a periosteum, upon which the tooth as a whole 
like other bones of the body, depends for nourishment 
and protection. 

The tooth-pulp, like bone-marrow, is generously 
equipped with a vascular and nerve supply which enables 
it, in turn, to feed and nourish the mineral constituency 
of its surrounding bony encasement — the dentine. It is a 
very highly sentient organ; and, morphologically speak- 
ing, may quite properly be considered an analogue of bone- 
marrow. 

The dentine, or bony substance of the tooth, is per- 
meated throughout its matrix with fibrils leading from the 
tooth-pulp, by means of which it is vitalized and kept in 
good repair. 

External Influences. — The teeth are greatly ex- 
posed to external irritant factors, which serve as exciting 
causes in the production of pathological conditions. 
Especially will this be true when the vitality of the tooth- 
pulp or dentine has become lowered by any constitutional 
dyscrasia. 



203 URIC ACID AND ITS CONGENERS. 

In no other part of the body do we find the organs 
subjected to such extreme thermal and chemical changes 
as in the oral cavity, where the teeth are exposed by direct 
contact to sweet and salt substances, to hot and cold 
liquids, acids, alkalies, etc. 

Protection. — Ordinarily, when the organism is in 
its normally healthy condition, and the teeth are in good 
repair, the lime (phosphate and carbonate) and other in- 
organic salts, which chiefly compose the dentine, are in 
such proportion to its organic constituents (7 to 3) that 
adequate protection is afforded the delicate internal tis- 
sues of the tooth against these deleterious external in- 
fluences — for, of course, only the dentine and its enamel 
are exposed by direct contact. 

Under these circumstances, the healthy dentine, for 
instance, owing to its peculiar composition, is a poor 
thermal conductor, and prevents the transmission of hot 
and cold waves to the pulp and, in this way, saves it from 
such forms of irritation. The same may be said concern- 
ing the effect of sweet and salt substances, acids, etc. 

But, on the other hand, should the proper kind and 
amount of nutriment to the dentine (from the general blood 
supply) be withheld or interfered with in any way, thereby 
changing the normal proportion of its mineral and organic 
constituents, it will at once be seen that its degree of con- 
ductivity may be altered in such manner as to permit trans- 
mission of thermal, chemical or mechanical impulses, and 
by such means seriously injure the delicate and sentient 
tissue of the pulp. 

The importance of this kind of protection is often 
made manifest to us when improper filling is used in a 
carious cavity. For example, if a metal filling (such as 



DENTAL CONDITIONS. 209 

gold) be fitted, the pulp often becomes irritated from these 
external influences, as evidenced by the violent pain and 
ache of the part — for metallic substances serve as a good 
conductor. But, if such filling be removed and a poor 
conductor substituted, such as gutta percha or oxyphos- 
phate cement, the pain immediately ceases, as has frequent- 
ly been demonstrated in actual practice. So long as a liv- 
ing pulp exists in a carious tooth, it should be protected 
by such filling-device as corresponds most closely to the 
composition of normal dentine. 

Decay. — A further point to be considered in the cases 
above described, in which the dentine is illy nourished, — is 
its susceptibility to decay. If its supply of nutriment from 
the general circulation (through the medium of the pulp 
arterioles) be inadequate or vitiated, the phosphates and 
carbonates, as well as the organic matter, both of which 
are so essential to the stability of bone structure, will be- 
come deteriorated in quality or quantity — and disinte- 
gration eventually ensues from the effect of exposure to 
heat, pressure, acids, etc. In this way, by the softening and 
breaking down of the substance of dentine, a carious 
cavity develops and finally disorganization of the tooth- 
pulp itself, which has now become more or less exposed to 
the deleterious external influences from which it has been 
previously protected. In short, tooth-decay often origin- 
ates primarily from some systemic disorder. 

In an elaborate article, on the "Constitutional Causes 
of Tooth Decay," read by Prof. Eugene S. Talbot, of 
Chicago, before the Fourth International Dental Congress, 
Aug. 30, 1904, reference is made to several cases ob- 
served in actual practice, wherein some systemic disturb- 
ance was the obvious aetiological factor in the production 
of decay, among which we note the following, to wit: 



210 URIC ACID AND ITS CONGENERS. 

(i) "A woman, twenty-two years old, a lifelong 
patient, became pregnant. Her teeth, which had been in 
fine condition up to this period, decayed rapidly thereafter. 
Caries appeared around new fillings and many new cavi- 
ties occurred within twelve months." 

(2) "A man, forty-six years of age, a broker, had 
sound, healthy teeth, with few fillings, until an attack of 
nervous prostration consequent on business strain oc- 
curred, when his teeth decayed rapidly, softening so that 
the enamel could be removed like leather." 

(3) "A minister, thirty-eight years of age, with a 
fine set of teeth, broke down from overwork. After three 
years absence in France, he returned to America with 
every tooth decayed, twenty-one of his teeth having to 
be crowned." 

(4) "A woman of forty-six years had two sons and 
a daughter. The daughter, at eighteen, was attacked with 
peritonitis and died within a week, thereby plunging her 
mother into deep depression. The mother's teeth, pre- 
viously in good condition, presented in eight months many 
cavities." 

(5) "Miller (Cf. Dental Cosmos, March, 1904) 
mentions the case of a man forty-five years of age, who 
was in fair health with the exception of asthma and a 
rheumatic tendency, and who was the subject of a well- 
marked case of erosion." 

Many such cases might be cited, but the point to 
which we wish to direct attention here is the significant 
clinical fact that tooth-decay is often but the local ex- 
pression of the existence of some constitutional disturbance, 
during the progress of which the substance of dentine is 
rendered liable to disintegration (caries) owing to its fail- 



DENTAL CONDITIONS. 211 

ure to receive an adequate supply of bone nutriment to keep 
it in good repair and in a condition to resist external influ- 
ences, to which it is ever exposed. 

UricacidjEMIA. — Among the various systemic fac- 
tors, which are instrumental in checking the flow of blood 
through the vessels of the pulp, thereby preventing the 
conveyance of nutriment to the surrounding dentine (thus 
contributing to its death and decay), none is more common 
than that stage of purin excess which we have designated 
" uricacidaemic." 

In discussing this phase of the subject, it should not be 
forgotten that the teeth, as an integral part of the mam- 
malian organism, are dependent (like any other animal 
tissue) on the general circulation for a supply of nutriment. 
For this purpose, the tooth-pulp is furnished with its 
minute arterioles and nerves which branch off from the 
larger dental and alveolar vessels and pass through the 
foramen to each pulp. From these pulp-arterioles and 
nerves, in turn, myriads of microscopic filaments are given 
off to and permeate the matrix of the surrounding dentine. 

It was once thought that the pulp was simply a for- 
mative organ and that its mission ended with the for- 
mation of the tooth; but it is now known that it is a true 
vital organ and continues to nourish the dentine by means 
of its bloodvessels and nerves. The dentine, too, is known 
to be a living tissue, subject to all the changes which 
vitality gives to an organ — such as nutrition and recuper- 
ation. 

From all this, it will be seen that the tissues of the 
tooth must suffer from the consequences of capillary 
obstruction in that immediate neighborhood; and, like 
other bodily tissue, will be subject to deterioration of 



212 URIC ACID AND ITS CONGENERS. 

structure from lack of nutriment, owing to such ob- 
struction. 

That these end vessels of the teeth often contain their 
full quota of waste matter, which the system is attempting 
to eliminate, may be seen in the deleterious local effects 
produced when the salts of lead, iodine, or mercury have 
been introduced and are retained in the circulation. The 
"lead line" on the gums, "mercurialization," loosening of 
the teeth, local pain and tenderness, noted under these 
circumstances, are too well known to require further com- 
ment. 

Moreover, it is almost unnecessary to state in this 
connection, that the urate salts are also known to accumu- 
late in this locality and give rise to the accustomed effects. 
Stomatologists are now generally agreed that the urates 
have as strong a predilection for the gomphosis articu- 
lation and connective tissues of the teeth as for any other 
joint or tissue of the body. It should be understood, how- 
ever, that the effects produced from their presence in 
excess in the condition we are considering (i. e., the uric- 
acidaemic stage) are simply such as may arise from 
obstruction of the flow of blood in the vessels of the pulp. 

Toothache. — The first symptom complained of in 
the uricacidaemic stage of these dental conditions, is tooth- 
ache. Like the distension of the cerebral vessels causing 
headache, the pressure of the vessels (distended with 
urates) against the surrounding highly sentient pulp-tissue 
causes toothache. Owing, too, to the firm bony encase- 
ment in which the pulp is inclosed, there is little or no 
opportunity for expansion, and the resulting pain is cor- 
respondingly severe — the so-called "throbbing" tooth- 
ache, initiated suddenly from bodily exposure on a cold, 
windy day. 



DENTAL CONDITIONS. 213 

Inasmuch as in this primary stage, the dentine has not 
been deprived of its proper nutriment sufficiently long to 
cause disintegration of its tissue-structure, there may as 
yet be no evidence of erosion or caries, — no signs of begin- 
ning decay; consequently, the toothache sufferer points 
out to the doctor or dentist an apparently perfectly sound 
tooth as the source of his trouble. This sometimes leads 
to ludicrous mistakes on the part of the surgeon. He and 
the patient disagree as to which tooth is the real "acher" 
but the former is so positive that some other adjacent 
carious tooth is the cause of the disturbance that he ex- 
tracts the latter, only to learn afterwards that the patient 
was probably correct — for the "toothache" continues. 
Whenever an apparently sound tooth is pointed out in this 
way as being the "acher," it is a good plan to strengthen 
one's diagnosis by looking for other uricacidaemic signs 
elsewhere — as a scant, high-colored, overacid urine, and, 
instead of extracting this or some other guiltless member, 
the proper eliminative measures should be employed to 
clean out the obstructed capillaries, as in headache, back- 
ache, or any other lithaemic "ache" occurring elsewhere 
in the body. 

It sometimes happens that this form of uricacidaemic 
toothache will suddenly disappear the moment the nervous 
victim approaches the portals of the (to him) chamber of 
torture. His pain is gone and, oftentimes, he returns 
home without entering the surgeon's office. How is this 
phenomenon to be accounted for, in the cases we are 
considering ? Simply, that strong emotion, or fear, 
through vaso-motor control, causes the sudden emptying 
of the surface capillaries of face and head — as in the s ud- 
den pallor often seen in persons overcome with such 



214 URIC ACID AND ITS CONGENERS. 

emotions. The force with which these vessels are emptied 
may be sufficient to drive the uratic obstruction back 
through the foramen into the larger alveolar vessels, and 
thus temporarily relieve the distensive pressure and ache 
of the pulp, due to' such obstruction. It is, of course, likely 
to return as soon as the capillary circulation is restored and 
the urates again enter or attempt to enter, the pulp artery 
through the foramen. 

While the foregoing explanation is based largely on 
theoretical deductions, yet we know from an extended 
clinical experience that very many uricacidaemic patients 
complain of "toothache" as one of the troublesome sub- 
jective symptoms, and that the alkaline eliminative treat- 
ment affords the most satisfactory results. It is almost 
invariably accompanied with other subjective and object- 
ive signs of lithaemia, which likewise disappear under the 
treatment. For all practical purposes, therefore, it would 
seem wise to class this so-called "nervous," "functional," 
or "neuralgic" toothache under the same category as the 
other "aches" characteristic of uricacidaemia, and employ 
the same therapeutic resources. As these cases are often 
submitted for first aid to the physician, rather than to the 
dentist, opportunity is given for systemic treatment, where 
local measures can be of little avail, except to afford tem- 
porary relief of the pain. 

Later Stages. — Retention of urates in the pulp- 
arterioles, if long continued, results in the gradual dis- 
organization and decay of all the tissue-structures of which 
the tooth proper is composed. This is partly due to lack of 
an adequate supply of proper nutriment and finally to the 
direct irritation of the uratic deposits themselves. The 
illy-nourished dentine loses its proportion of calcium and 



DENTAL CONDITIONS. 215 

organic material, so essential to bone structure, and is thus 
more easily affected by external irritants: a cavity de- 
velops. The pulp, from lack of this bony protection, be- 
comes injured and is eventually inflamed and destroyed: 
the latter effect being due in great measure to the presence 
of deposits of urates, which in the later stages are thrown 
down. The inflammation also extends to the soft tissues, 
and such conditions as gingivitis, and, perhaps, alveolar 
abscess may supervene. In the words of the stomatologist, 
we have all the clinical signs characteristic of "gouty 
pericementitis." 

In the American Text-Book of Operative Dentistry 
(515-531), in the chapter on "Pyorrhea Alveolaris of 
Constitutional Origin," written by Prof. C. N. Peirce, of 
Philadelphia, the views of modern stomatologists concern- 
ing the influence of uric acid retention in the system in the 
production of many disorders of the teeth and gums, is 
given somewhat in detail; from which we note the follow- 
ing paragraph, on the effects of the uratic deposits in 
pyorrhea : 

"The deposit is the source of irritation which in most 
cases is followed by inflammation, leading to inflammatory 
degeneration and probably coagulation necrosis of the 
cellular elements. The alveolar walls melt down particle 
by particle, the pericementum disappears, the diseased 
area usually becomes infected by pyogenic organisms, and 
the process of suppuration is an additional factor leading 
to the exfoliation of the teeth. As in necrotic areas of other 
parts, calcareous deposits occur, which cover and almost 
entirely obscure the primary deposit of urates. * * * 
By the continued irritation of uratic deposition and the co- 
operation of micro-organisms, the inflammatory process 



216 URIC ACID AND ITS CONGENERS. 

extends until the membrane is destroyed to such an extent 
that it is no longer capable of nourishing and supporting 
the teeth. " 

The alkaline treatment (eliminative in character), in 
conjunction with the usual local measures, is recommended 
by this well-known authority. 



CHAPTER XXIV. 



haig's work. 



His Three Books. — To the writings of Alexander 
Haig, M.A., M.D. (Oxon.), F.R.C.P., of London, 
England, the profession is chiefly indebted for having 
brought the uric acid subject into the deserved promi- 
nence it holds. Aside from the numerous articles from his 
pen, which have appeared from time to time in English 
and American medical journals during the past few years, 
are the following three books, which have been read ex- 
tensively on both sides of the Atlantic; to wit: 

i. "Uric Acid as a Factor in the Causation of Dis- 
ease' ' — his main work: a cloth bound volume of 816 
pages, containing seventy-five cuts, which has now reached 
its seventh edition. 2. "UricAcid: An Epitome of the Sub- 
ject'' — a condensed statement of the main facts as they 
occur in his former work, and contains 158 pages. 3. 
"Diet and Food" — a little book of 138 pages, devoted 
entirely to purin-free foods in relation to " Strength and 
Power of Endurance, Training and Athletics." 

Their Popularity. — Haig's views, concerning the 
influence of uric acid in the causation of disease, have been 
adopted by the great body of practitioners who have read 
his main work. The popularity of this book is due in 
great measure to the evident deep sincerity of its author, 
to its general lack of technicalities, and its mass of con- 
vincing clinical experiments. 

Few medical works of recent times have appeared in 
which the subjects treated of have been presented in a 



218 URIC ACID AND ITS CONGENERS. 

more readable form. The language is plain, and the 
thoughts of the author are made so clear that a tyro could 
readily grasp his meaning. His strong convictions are 
patent in every page; every paragraph; every sentence. 
The fact, too, that he has himself been the subject of 
many of his experiments gives added weight to his inter- 
pretation of the findings. For many years, he was the 
victim of severe headaches and it is to his studies into the 
causes of these headaches and their treatment that he was 
led to the discovery of the most important facts concerning 
uric acid. One discovery led to another, until finally, he 
reached the conclusions which he now so convincingly 
brings out in his main work. His theories, indeed, are 
argued with such inherent faith, that they appear more in 
the nature of established facts. 
/ His Theory. — Haig is of the opinion that if the raw 
material (nucleins and purins), from which exogenous uric 
acid is derived, be entirely cut off from the food which we 
ingest, the body will have no trouble in taking care of that 
other portion of uric acid (endogenous), which is derived 
from muscle metabolism and the breaking down of the 
tissue cells within the organism. He firmly believes that 
the various uric acid troubles which afflict mankind are 
due to the introduction of "food poisons"; and, that, if 
care be taken to ingest purin-free foods only, the organism 
will be enabled to eventually rid itself of the accumulation 
of stored-up urates in the tissues, and remain in a healthy 
condition thereafterward — i. e., so far as uric acid is con- 
cerned, and provided no more "raw material" is ingested. 
He has consequently become a strict vegetarian, himself,, 
and strongly advises all of his uric acid patients (and their 
number is by no means small) to follow his example. He 



HAIG'S WORK. 219 

claims that, by this means, his own sufferings have been 
made to disappear, as well as the sufferings of hundreds of 
others. 

Concerning Drug Action. — Haig classifies all uric 
acid disorders under two heads; viz.: 

I. Collaemic. 2. Arthritic. 

In disorders of the former class, the urates are still in 
the blood, and the symptoms are caused by the blocking 
up of the capillaries with uric acid in a colloid, gluey, or 
semi-gelatinous form. In those of the latter class, the 
urates have been precipitated out into the tissues, there- 
fore the blood is temporarily freed of uric acid. 

He classes uric acid remedies under two heads; viz.: 
I. Solvents (heat and alkalies). 2. Precipitants (cold and 
acids). 

By means of the "precipitant" remedy, disorders of 
the "collaemic" class (headaches, etc.) are relieved, owing 
to the driving out of uric acid from the blood into the 
tissues. By means of the "solvent" remedy, disorders of 
the "arthritic" class -(rheumatism, etc.) are relieved, 
owing to the resorption of uric acid from the tissues into 
the blood. 

He says: "There is thus a law that all local precipi- 
tation diseases are relieved by solvents, and that all col- 
laemic diseases are relieved by precipitants; in other 
words, by those things which clear uric acid out of the 
blood and drive it into the fibrous tissues — these being but 
two sides of the same process. More than this, by the ad- 
ministration of solvents or precipitants, we can produce at 
pleasure a member, either of the collaemic or of the arthri- 
tic group, and change the one for the other at will. Indeed 
I very frequently ask patients which they prefer to have, as 



220 URIC ACID AND ITS CONGENERS. 

I know that in curing the one I must produce the other. 
In serious cases, there is, of course, no choice — one must 
choose that which is least deadly to life, and that is gener- 
ally a member of the arthritic group." — (Uric Acid: An 
Epitome of the Subject, iio-iii). 

Adverse Criticism. — It will be seen that Haig uses 
drugs for their temporary effects only. He places his reli- 
ance chiefly on rigid dietary rules. But we must strongly 
and adversely criticize his statement: — "J know that 
in curing the one I must produce the other." 

It is true, that when the solvent remedv is used in the 
treatment of rheumatism, — collaemic symptoms (such as 
headache) will be temporarily produced while the urates 
are passing en route through the blood. But if this sol- 
vent remedy be at the same time an el'iminant remedy, the 
urates, instead of remaining in the blood, are excreted 
from the body by way of kidneys and bowels. The col- 
laemic, as well as arthritic symptoms, therefore, will dis- 
appear when the excess of urates is thus removed. By 
this method of treatment, we not only drive the urates out 
of the tissues into the blood, but out of the body entirely. 
This has been clinically demonstrated to the satisfaction of 
hundreds of physicians and their patients. 

Again, Haig is decidedly wrong, in recommending 
"precipitant" remedies at all. The idea that uric acid 
headaches can be cured only by driving the urates out of 
the blood into the tissues, thus producing rheumatism, is 
an extremely narrow view to take. On the contrary, in- 
stead of precipitating the urates out of partial solution or 
suspension, our object should be to render them even more 
soluble, and, at the same time, aid the excretory organs in 
their function of elimination. That is, bv means of a 



HAIG'S WORK. 221 

remedy, which increases the alkalinity of the blood, we also 
render the latter less viscous and the colloid or gelatinous 
urates, which block up the capillaries, are changed thereby 
into a more soluble, aqueous form, and may be convey- 
ed in this way, in solution, to the kidneys and excreted in 
the urine, which has itself been made less acid and a 
better solvent of urates in consequence. Thus, we not 
only remove the cause of the headaches (as Haig does), 
but we avoid producing the rheumatism (which Haig does 
not). 

As physicians, we should not become blinded to the 
fact, that a person may stop ingesting "food poisons" and 
yet suffer from the ill effects of these same "food poisons" 
which he has previously ingested. It would be irrational 
to claim, that the only way to cure a case of opium poison- 
ing is to withhold the further introduction of opium. We 
are not yet willing to admit that there is no therapeutic 
efficacy in prescribing an "antidote" in such cases. On 
the other hand, it must be admitted by Haig that it is not 
always possible, in actual practice, to prevent the ingestion 
of purin-containing foods. Are we then, in truth, per- 
forced to accept his dictum: "I know that in curing the 
one I must produce the other ?" " Must" (in some cases) 
"produce the other" (temporarily), he might better have 
said. 

His Mistake. — In demonstrating so clearly to the 
medical world the influence of uric acid as a factor in the 
causation of disease, Haig has accomplished a work that 
will cause posterity to enroll his name in a list with such 
men as Liebig, Virchow, Niemeyer, Pasteur, Koch, and 
other discoverers of some fact or phenomenon of medical 
importance. But, like the discoverers of a hitherto un- 



222 URIC ACID AND ITS CONGENERS. 

known continent, he has fallen into the temptation of at- 
tempting too much: he has made an impossible effort to 
sound all channels, scale every mountain peak, find the 
source and delta of every stream, look into every inlet and 
harbor for a safe anchorage, etc. 

His mistake is in setting out personally upon more ex- 
ploring expeditions than any single individual could possi- 
bly complete in a satisfactory manner and which should 
have been left for others who were not thus handicapped, 
and who were better situated or more thoroughly equipped 
to perform the work properly. 

Haig is not a chemist. Some of his subsidiary theo- 
ries, based upon far-fetched chemical speculations, are 
distinctly amusing, or would be, if such credence were not 
given to his every opinion by the general practitioner. It 
is owing to some of the crude chemical methods he em- 
ploys, and the remarkable therapeutic conclusions derived 
from them, that his entire work has been derided by the 
physio-chemist and other specialists. They have summed 
up the whole by judging of some of the unessential parts. 
This is unfortunate, as well as unfair, for it has led to a 
much underestimated opinion in certain scientific quarters, 
of the value of Haig's work. 

A Singular Contradiction. — In his effort to dis- 
cover some chemical fact that would fit in with one of his 
subsidiary therapeutic theories, Haig not only makes an 
inexcusable physiological blunder, but contradicts himself 
in a most remarkable manner. He is trying to explain 
how lithia relieves arthritis, and yet, at the same time, 
combines in the body with the phosphates, thus causing 
retention and a lessened excretion of uric acid in the urine. 

He refers to an ancient chemical treatise, (Rose), in 
* which he found it stated that, in the laboratory, lithia 



HAIG'S WORK. 223 

" forms a nearly insoluble triple phosphate with hypophos- 
phate of soda, or with the triple phosphate of ammonia 
and soda — salts generally present in animal fluids." He 
jumps to the conclusion that lithia, when introduced into 
the circulation, probably forms a chemical combination in 
the nature of these "triple phosphates" and "thus puts 
out of use" a certain amount of soda phosphate, which 
normally holds uric acid in solution in the blood. He 
forgets that these so-called triple phosphates, "in animal 
fluids," are those of magnesium and ammonia which are 
found in the urine after voidance and after decomposition 
has taken place, when the "earthy" phosphates (magne- 
sium and calcium) are formed, which, being insoluble, 
are thrown down as a precipitate. It will thus be seen how 
far-fetched is the chemical fact which he found that would 
apparently satisfy the demands of his therapeutic theory. 
But, still more surprising is the following statement 
which he makes: "Lithia, then, relieves arthritis by clear- 
ing the blood of uric acid, but not, as was supposed, by 
eliminating uric acid from the body. We now see that it 
clears the blood, but retains uric acid in the body." (Uric 
Acid as a Factor in the Causation of Disease, Fifth edition, 

p- 58)- 

Relieves arthritis, by driving uric acid out of the blood 
into the tissues! He here stultifies himself and contra- 
dicts his main theory, which appears repeatedly through- 
out this same work. His chief contention is, and has 
always been, that any drug, which clears the blood of uric 
acid by driving it into the tissues, causes arthritis. In this, 
he is doubtless correct. It would appear, that in order to 
bolster his unimportant notion regarding the therapeutic 
action of lithia, he flatly contradicts himself. It is largely 



224 URIC ACID AND ITS CONGENERS. 

owing to these chemical idiosyncrasies, which he has al- 
lowed to creep into his work, that Haig's reputation as a 
scientist has been made to suffer from the unfriendly pens 
of numerous writers. 

Notwithstanding these minor faults, it is doubtful if 
any scientific medical work of modern times contains so 
many important practical truths, or points out so many 
significant clinical facts, as does this remarkable work of 
Haig. 

Value to the Clinical Worker. — While Haig's 
well-known "vegetarian" views will probably never be- 
come generally accepted, nor his rigid dietary treatment 
followed out to the letter, yet much practical good will 
result from his having attracted so much attention to the 
subject. The beneficial results he has obtained, by cutting 
off entirely the food source of exogenous uric acid, can 
only serve to emphasize in the physician's mind the im- 
portance of interdicting certain well-known purin-foods in 
the dietary which he allows his patient. But it should not 
be forgotten that even the amount of endogenous uric acid 
normally formed within the body may become excessive, 
if not properly eliminated, or if the liver becomes tempor- 
arily disabled and fails to oxidize into urea its due propor- 
tion (50 per cent.) of uric acid formed from day to day, 
Nor should we forget that some undue muscular effort or 
exposure of the surface of the body to a sudden chill, may 
cause precipitation of the urates in a given locality thus 
exposed, even though uric acid be present in but slight 
excess over the normal amount. 

One great value of Haig's work lies in the clearness 
and thoroughness with which he has demonstrated how 
uric acid, by obstructing the capillary circulation, thus 



HAIG'S WORK. 225 

slowing the capillary reflux and causing increased blood- 
pressure, may become the exciting factor in the production 
of so many circulatory diseases. That it does so impede 
the flow of blood, he has proven conclusively. 

Prof. Haig's experiments upon himself, and others, 
whereby he has clinically demonstrated by means of "pre- 
cipitant" and "solvent" remedies that he can actually 
produce one or the other class of uric acid disorders, at 
will, are exceedingly interesting and instructive. In other 
words, he has shown that simply by "clearing the blood" 
of uric acid by precipitating the same into the tissues, and 
vice versa, he can reproduce the very diseases that occur in 
the natural course of events : thus pointing out the fact that 
the things in Nature which act as precipitants (cold and 
acids), serve to lessen the blood's alkalescence and cause 
the precipitation of urates, resulting in rheumatic symp- 
toms; while, on the other hand, those that act as solvents 
(heat and alkalies) serve to increase the blood's alkales- 
cence and cause the resorption of urates from the tissues, 
relieving the rheumatic symptoms and producing those of 
the uricacidaemic type, unless the urates are removed from 
the circulation by way of the excretory organs. It is in 
aiding the performance of this latter function that the work 
of the physician may appear in evidence. 



CHAPTER XXV. 



THE FOOD QUESTION. 



Effect of Environment. — In the never-ending 
struggle for existence, all organic living forms, whether of 
the animal or vegetable kingdom, are constantly reacting 
with, and adapting themselves to, their environment, upon 
which they are dependent for sustenance. This environ- 
ment may be limited to a square foot of soil, as in the case 
of the plant, or extended to a square mile or more, as in 
the case of many animals and some of the human kind, 
or may include a greater part of the earth's surface, as in 
the case of the most enlightened modern peoples with 
international facilities. But, owing to the trouble and 
expense incurred in obtaining food-substances from a dis- 
tance, the great mass of human beings look to their more 
immediate environment for sustenance. As such environ- 
ment varies in different zones of the earth, so does the 
character of the food vary among the different nations. 

Moreover, it will be observed that the fauna and flora, 
from which sustenance is derived, are always appropriate 
to the peculiar needs of the organism (in its struggle for 
existence) in that particular locality. For example, the 
climatic environment of the Esquimau requires him to 
avail himself of the adipose-producing (heat-retaining) 
hydrocarbon elements in food, which he finds ready to 
hand in the lower cryptogams, and oil and blubber-bearing 
piscatorial denizens of that region. The indolent dwellers 
in torrid regions, on the other hand, find in the fruits of 
their luxuriant flora the carbo-hydrate element ready 



THE FOOD QUESTION. 227 

prepared, requiring little exertion on theirpart to obtain it, 
thus obviating the necessity of so much nitrogenous (energy- 
producing) food in the struggle for existence. 

Owing to the character of their environment (there 
being a meager fauna) the nations of the East have been 
forced to obtain the nitrogenous element in food chiefly 
from the vegetable kingdom (rice); though the palates of 
the wealthier class are pampered with purin-delicacies, 
obtained from both the animal and vegetable world, — as 
the roe of the sturgeon and the alkaloid of the tea-plant, 
so highly prized by the Chinese. The purin-alkaloid of the 
coffee bean is used in a similar manner by other vege- 
tarian peoples. 

The highly civilized peoples of the temperate zones of 
the earth still hold largely to the nitrogenous foods of 
animal origin, entailed as a legacy from their ancestors. 
The settlers of England and America, during the first 
century or two, were confronted with an environment that 
required hard work and they found a rich fauna, which 
furnished the nitrogenous food-elements essential to the 
performance of such work. It was natural, right and 
proper that our ancestors should avail themselves of "the 
goods the gods provided," and thereby, in their hard strug- 
gle for existence, obtain essential nitrogenous fuel at the 
minimum expenditure of energy: in this way, not only 
ridding the forest of these troublesome and dangerous 
denizens, but gaining strength whereby to clear away the 
forest itself and pave the way for future fertile acres, as 
well as populous cities and towns. 

From what has been said, it will be seen that what 
serves as adequate sustenance for the people of one zone 
may not be sufficient for those of another. The Japanese 



228 URIC ACID AND ITS CONGENERS. 

have proved that foods derived from the vegetable world, 
when coupled with temperate habits of eating and drinking, 
tend to produce a hardy and vigorous race but this does 
not necessarily mean that such vegetable-feeding is the best 
for the Englishman or the American, whose progenitors 
for ages have been accustomed to a quite different mode of 
living. While the Englishman or the American may, 
doubtless, with advantage, cut down his purin-luxuries to 
the level of the Japanese, it would be a dangerous experi- 
ment for either of the former to attempt to deprive himself, 
all at once, of the nitrogenous food of animal origin to 
which his digestive apparatus has become so completely 
adjusted. 

It would seem, therefore, that man assimilates from 
his environment that which is obtained along the lines of 
least resistance, so that different geographical groups of 
people thrive best on their own particular foods, to which 
their organs of digestion and assimilation have attuned 
themselves. This is similar in a general way to what we 
see in contrasting the foods of the different animal species 
— the bulkv herbivorous mammal thriving on vegetable 
matter that the little rodent would starve upon. 

Vegetarianism. — The facts above mentioned have 
been referred to here in order to point out one of the rea- 
sons why the English speaking peoples, as a rule, have 
carnivorous proclivities — i. e., through the force of en- 
vironment as well as hereditary descent. Enough has been 
said to indicate that it would be unphysiological to attempt 
to change all this in a day: that is, for the entire nation 
to suddenly become "vegetarians," as some misguided 
enthusiasts suggest, for, as may be seen, our nutritious 
needs and digestive capacity have been molded into their 



THE FOOD QUESTION. 229 

present shape as an inevitable result of the reaction of the 
parent organism with the environment. 

Though " meat-eating" has borne so conspicuous a 
part in the development of our people, we cannot be 
accused of selecting the flesh of carnivorous animals for 
food, as do some of the vegetarian peoples when desiring a 
"delicacy." With the exception of fish (and possibly 
pork), the Anglo-Saxon restricts his choice to vegetable- 
feeding animals. And even though the vegetarian Chinese 
eat ypung cats and dogs, as delicacies, yet the animals are 
quickly fattened on a vegetable food — rice. The natives of 
Hawaii serve baked dog as a table luxury, but, here, too, 
the animal is fattened on a vegetable tuber, taro, in the 
form of "poi." The result, in both cases, is a tender and 
toothsome meat, much like pork. 

Modern Conditions. — The environment of our 
ancestors of a hundred years ago, was quite different from 
that to which the organism must adapt itself today, es- 
pecially in the more populous centers. While our sturdy 
forefathers had a restricted environment, from which 
they selected the muscle-fuel most needed in their struggle 
for existence, we have an almost unlimited environment 
which furnishes fuel of every kind to meet the varied re- 
quirements of modern life. 

Moreover, it must be remembered that evolutionary 
change has been going on, not only in our sociological 
development, where men are engaged in entirely different 
pursuits, mental and physical, but in the physiological 
needs of our organism, which must undergo corresponding 
change. A century or more ago, men struggled along very 
nearly the same lines, and their food requirements were 
very much alike. Today, the inhabitants of a single state 



230 URIC ACID AND ITS CONGENERS. 

are so differently conditioned in the struggle, that it would 
not be a stretch of the imagination to class them under 
different species — from a physiological standpoint. Their 
conditions in life may be so widely different, that two men 
residing in the same American city may be further apart in 
their food-requirements, than is the average American 
from the Chinaman. 

While, therefore, it will be seen that "what was good 
enough for father, is good enough for me," is hardly a safe 
guide for correct eating, neither is it practicable to lay 
down any specific feeding-rule (such as "vegetarianism") 
that all can follow. Our environment, which has grown so 
enormously in its complexity, necessitates a corresponding 
growth in the ability of the reacting agents to adapt them- 
selves to this changed condition and he, who would not 
fall by the wayside, must train his organism to meet these 
varied requirements. In a general way, a mixed regi- 
men is essential, but, owing to the division of labor in 
highly civilized communities, the amount and relative 
proportion of the ingredients will vary, according to men- 
tal and physical requirements, — the nitrogenous element 
(of animal origin) predominating in one case and that of 
vegetable origin in another, carbo-hydrate material in an- 
other, much of the inorganic salts in another, fat in an- 
other, etc. In short, no single menu will answer the pur- 
pose for all, nor for the same individual at all times. 

Purin Feeding. — While our parents necessarily in- 
gested a certain proportion of purin-substances with their 
meat-eating, it is doubtful if they introduced into their 
system in this way much more waste extractive than do 
the vegetarian peoples, with their purin tea, coffee, etc., 
and, even if they did, their physical activity and out-of- 



THE FOOD QUESTION. 231 

door life served to keep open the avenues of escape and 
prevent accumulation. Meat was eaten for sustenance: 
for the strength-giving properties of its muscular tissue. 
The sweetbreads, fries, and other glandular organs were 
thrown away. What are now considered purin-delicacies 
were then deemed unfit to eat. 

The great packing houses of the "beef trust," today, 
make up into "food" every portion of the animal, from the 
tip of his nose to the heel of his hoof, and all this is "pre- 
served" or "canned" and sent broadcast throughout the 
land. Nothing is wasted, not even the blood. It is said 
that the only part of the pig which is not turned into 
account, is his "squeal"! 

And there is a constantly growing demand for all 
these so-called "purin-delicacies." The chefs of the great 
city hotels, restaurants, rathskellers, and private palaces, 
have become very expert in concocting animal refuse into 
"toothsome" dishes to tickle the palate of the after- 
theater and other midnight patrons, who are out in quest, 
not of food, but something in the way of a "fourth meal" 
that can be washed down with a relish. 

Why is this ? Simply because there are so many 
supernumerary individuals born today whose struggle 
for existence consists in the mere search for something to 
pander to an appetite that has become depraved through 
the lack of necessity to perform any legitimate object in 
life. But the stern laws of Nature will eventually rid the 
earth of such incumbrances. This will be done through 
disease. The man who overloads his blood with fuel 
that cannot be utilized, must sooner or later bank the fire 
and much more so he who shovels in ashes and clinkers at 
the same time. 



232 URIC ACID AND ITS CONGENERS. 

If these pleasure-seeking supernumeraries were the 
only people to thus destroy themselves, no harm would be 
done but, unfortunately, the enormous quantity of purin- 
stuff in the market and the success of modern cookery in 
preparing animal refuse in palatable form, has resulted in 
establishing the pernicious purin-eating habit. Many 
people indulge in these dishes under the mistaken notion 
that they are ingesting nitrogenous nutriment in concen- 
trated form. By thus loading the system with animal 
purins in food-stuff, and vegetable purins in table-drinks 
(tea and coffee), taken in conjunction with over-feeding 
and a sedentary life, it is not surprising that gout, rheuma- 
tism, and other metabolic disorders are becoming so prev- 
alent. 

The Remedy. — Instead of committing the people to 
"vegetarianism" exclusively, the physiological remedy 
lies in the direction of a purin-free mixed diet. Man, as 
the highest of the mammalian scale — surrounded with 
the most complex environment and having the most com- 
plex organism by which to adapt himself — is not meant to 
become an herbivorous animal nor to feed on fruits and 
nuts, like the frugivorous or granivorous rodent, nor on 
flesh food, like the carnivora: — He is capable of living on 
all and is entitled to the best of all. 

If the same care and skill that has been shown by the 
"beef trust" and expert chefs in utilizing all animal refuse 
for food, were given toward removing all purin-waste from 
meat that is to be eaten, a kind of sustenance would re- 
main, not only capable of easy digestion but furnishing 
nitrogenous food-elements in the most acceptable form. 
Of course, the proportion of flesh-food of this kind which 
should be combined with the nitrogen and carbo-hydrates 



THE FOOD QUESTION. 233 

of the vegetable kingdom to make up the proper mixed 
regimen, would depend on the needs of the organism of 
each individual — i. e., whether his nerve-force or muscle- 
energy needed replenishing chiefly; and this would de- 
pend largely on his vocation and manner of living. 

A system of food-education is needed. The govern- 
ment should see that all foods manufactured or prepared 
for public use should be free not only from so-called 
"poisons" but from so-called "purins," which are almost 
equally poisonous or, at least, almost equally toxaemic. 
Chefs should be required to educate themselves along the 
lines of proper food preparation, just as the druggist is 
required to understand the compounding of medicines — 
using the "poison" or "danger" label on goods that call 
for it. The people, themselves, should be instructed in 
the public-school course, learning the composition of food 
substances, so as to be enabled to determine the propor- 
tion of each element in a mixed regimen, which may be 
physiologically indicated in a given case. 

While all this may seem visionary; yet, as evolution- 
ary progress points toward the desirability of such know- 
ledge, we can see no reason why it may not come to pass 
sometime in the distant future. At all events, the neces- 
sity for self-defense becomes more urgent as the competition 
in the struggle for existence grows keener, from day to day; 
and the time approaches when the minority will be de- 
feated, — i. e., they who fight for personal wealth at the 
expense of the public health. 



CHAPTER XXVI. 

DIETETICS. 

General Rules. — In the dietetic treatment of 
"purin excess," the general practitioner seldom finds two 
patients thus afflicted who require exactly the same regi- 
men but he will find many cases wherein certain food- 
substances should always be interdicted and in which 
certain general rules will always apply, for example: 

i. No exogenous purins should be needlessly intro- 
duced into the organism. 

2. No article of food nor drink should be ingested that 
causes gastro-intestinal fermentation, flatulence, epigas- 
tric distress, constipation, or insomnia, in a given case. 

3. The daily quantity of food ingested should never 
exceed the digestive capacity of the patient; while the 
quantity digested should never be in excess of the daily 
physiologic needs of the organism. 

4. A mixed regimen (both animal and vegetable) is 
usually indicated. 

5. The proportion of flesh food allowed should de- 
pend on muscular requirements. 

6. No acid food nor drink should be allowed, nor any 
food, drink, medicine, etc., which lowers the blood's al- 
kalescence or increases the acidity of the urine. 

7. With the above exceptions, the dietary should 
correspond in a general way with that to which the patient 
has long been accustomed. 

If it be true that the symptoms complained of in a 
given case are due primarily to the failure of the organism. 



DIETETICS. 235 

from one cause or another, to free itself of purin-waste 
properly, so as to prevent capillary obstruction or con- 
sequent uratic depostion, then it is obviously the duty of 
the physician to see that his patient does not introduce 
purin food-products unnecessarily into the system; for 
it is manifest that our medicinal means will prove more 
effective in aiding the organism to rid itself of an excess, 
provided such excess is not increased by an extraneous 
supply. 

As carbo-hydrate feeding is contraindicated in dia- 
betes, so are purin-containing foods contraindicated in 
purin excess. In one case, we wish to cut off the supply of 
raw material from which sugar is manufactured within the 
system; in the other the raw material from which uric 
acid is obtained. Practical experience has shown that 
bread, potatoes, other starchy foods and sweet materials, 
aggravate the diabetic symptoms; while, it has been like- 
wise demonstrated that fried meats, meat soups, extracts, 
gravies, coffee, tea, acid foods and drinks, aggravate the 
uricacidaemic, rheumatic, or gouty symptoms. In one case, 
the trouble appears to be due to faulty carbo-hydrate 
metabolism; whereas, in the other, purin catabolism and 
elimination seem to be at fault. 

Uricacid^mic Patients. — Inasmuch as the symp- 
toms in the primary stage are often transient in character, 
being those caused chiefly by an impeded flow of the blood- 
current through the capillaries, resulting in local pain 
from distension and pressure, and in sluggish action in the 
tissue cells from accumulation of waste, — it will be seen 
that the principal therapeutic indication is to remove the 
obstruction at once by conveying it away in the circulation. 
This uratic impediment, being as yet in non-crystalline 



236 URIC ACID AND ITS CONGENERS. 

form, can usually be taken up and removed in a short 
time. The patient, therefore, may well afford to deny 
himself of certain table-luxuries, or even what he con- 
siders table-necessities for a few days, if he is assured of 
obtaining more speedy relief of the symptoms thereby. 

The less the amount of nutrient material introduced 
into the blood-stream at this time (during the few days 
referred to) — i. e., the less solid or semi-solid matter to be 
conveyed by the circulating medium through the capillar- 
ies — the more dilute will be the blood and consequently a 
better solvent by which to take up the obstruction and 
remove it. In short, the freer the circulation of food 
products (even though the latter be assimilable) the greater 
the opportunity for purging itself; in other words, the 
blood should never be overloaded with chylous nutriment 
at these times. 

From this it will be seen that the diet of the uricacid- 
aemic patient, during the treatment of the acute symptoms, 
as an attack of migraine, should not only be comparatively 
free from purin-containing substances but considerably 
restricted in the daily quantity of other foods allowed, 
especially tissue-making material — nitrogenous foods. 
Such carbo-hydrate materials as contain the alkaline salts 
or organic acid bases which are known to combine with the 
carbonates of the blood and form alkaline salts, are in- 
dicated — such as the citrates in many garden fruits. 
Foods containing starch and sugar should not be eaten in 
sufficient quantity to cause gastric fermentation. In order 
that the alkalies contained in them may combine as bases 
with the free uric acid in the urine, such vegetables as 
cabbage, cauliflower, turnips, spinach, etc., may be eaten 
by patients subject to gravel or calculi. Alkaline drinks, 



DIETETICS. 237 

(vichy, soda) or lime juice and water should be recom- 
mended, as well as plenty of plain water. 

A very good menu may be selected from the following 
articles, for breakfast: — cornmeal mush, oatmeal gruel, 
gluten cakes, soft-boiled egg, stewed prunes (sweetened 
with saccharine, dissolved in water before preserving), 
"poi" cocktail. 

For dinner or luncheon: — raw oysters, little neck 
clams, ripe olives, vermicelli soup, vegetable soup with 
rice, boiled brook fish, roasted fowl, baked potato, 
squash, turnip, carrots, new corn, lettuce, spinach, 
custards, tapioca. It is, of course, understood that the 
patient is to indulge sparingly and that any idiosyncrasy 
is to be respected. 

Rheumatic Patients. — In the secondary stage of 
purin excess, the circulation becomes, from time to time, 
comparatively free from uratic waste owing to its precipi- 
tation out of solution and consequent deposition into the 
tissues; but, as the blood speedily regains its normal al- 
kalinity after such temporary withdrawal of urates, the 
latter are resorbed into the circulation which again be- 
comes subalkaline and the urates are once more thrown 
out of solution and deposited in the tissues at some other 
locality: and thus the process continues (deposition, re- 
sorption; deposition, resorption) until Nature, herself, 
succeeds unaided in eliminating the urates from the sys- 
tem via the urine (i. e., by repeated "explosions"), or 
until aid is furnished by means of a rational dietetic and 
medicinal treatment. 

It will be seen, therefore, that the same general plan 
of feeding may be recommended for the relief of acute 
attacks, or exacerbations, here, as has already been sug- 



238 URIC ACID AND ITS CONGENERS. 

gested for the removal of capillary obstruction in the 
primary stage. That is, the blood-stream should be bur- 
dened with as little chylous nutriment as possible under the 
circumstances, and, as far as practicable, should be fur- 
nished with no exogenous purins nor other material that 
tends to acidulate. The rules regarding the quality and 
quantity of foods ingested, are equally applicable in both 
cases — i. e., during the two or three days', or a week's 
treatment. 

Chronic Cases. — While the above-recommended re- 
stricted diet (or one even much more restricted) may be 
insisted upon for a brief period, and directions will usually 
be religiously observed by the patient, during the few 
days essential to the handling of his case until subsidence of 
the acute symptoms, yet it will be found that in the pro- 
phylactic treatment of such cases, as well as in the more 
prolonged treatment of chronic cases, that a somewhat 
different feeding-plan must be adopted. 

Physicians will readily recognize that the rheumatic 
stage of purin excess furnishes more chronic cases, ob- 
stinate to treatment, than all other disease-processes com- 
bined. The patient has usually reached an age when 
habits have become firmly rooted, and which, in the great 
majority of instances, cannot be suddenly uprooted nor 
radically altered without injury. Immediate denial of 
many or all of the accustomed table-viands may be found 
necessary to the treatment indicated at the time of an 
exacerbation of the symptoms and will generally prove 
satisfactory in results, but it would be impracticable and, 
perhaps, disastrous, to attempt the same thing in those 
cases in which we wish to establish a more prolonged, 
possibly, permanent dietary. 



DIETETICS. 239 

In the cases under discussion, the patient is not us- 
ually bed-ridden, but is enabled to be up and around and, 
probably, to attend to business. We refer to the so-called 
" office patient," in whose case the trouble may have ex- 
isted for one year, ten years or more. "Stiffness" in 
muscle or joint, "aches and pains" in various localities, 
constipation, "biliousness," etc., are some of the symp- 
toms commonly complained of. 

In our efforts to afford substantial relief in these cases, 
we may greatly aid the therapeutic measures employed by 
combining the same with a rational dietary. If the patient 
always gained an intelligent comprehension of his physi- 
cian's wishes in this matter, and a feeding-plan were sug- 
gested that could be followed out in a given case and ob- 
servations made that directions were being obeyed, — the 
question of "diet" would no longer remain relegated to 
the position of neglect it now occupies in the clinical hand- 
ling of these "chronic" cases of the rheumatic stage. 

One of the most significant modifications that can be 
made with profit in the. dietary of most of these patients is 
a reduction in the daily quantity of food ingested. In a 
paper, on "The Importance of a Study of Nutrition," 
read before the New York Academy of Medicine, Oct. 9, 
1905, Prof. R. H. Chittenden, of Yale, says: 'There is a 
great tendency to an overaccumulation of reserve material 
in the blood. It is easy, in enriching the blood by food, to 
overenrich it, to cause, through oversupply of food mater- 
ial too much chyle and other material to enter the blood. 
My own observations in this direction, continued now for 
several years, lead me to believe that there is much of value 
to be learned in a study of the minimal quantities of food 
required to maintain health and strength. The real needs 



240 URIC ACID AND ITS CONGENERS. 

of the body for food are unquestionably much below the 
amounts ordinarily consumed and, this being true, one 
may well ask the question, does not this excess of food, for 
which the body has no physiologic need, in the long run 
imperil the health of the individual, diminish the ordinary 
powers of resistance, and so pave the way for various 
forms of disordered nutrition, which we speak of as dis- 
ease?" (Cf. American Medicine, Nov. II, 1905, p. 818). 

From his elaborate feeding experiments, which have 
so attracted the attention of the scientific world, Prof. 
Chittenden has proven that but little more than one-half 
the total amount of nitrogen hitherto deemed absolutely 
essential to physiologic needs, is required to maintain 
health and strength to the highest degree. However, we 
have long felt positive that one of the principal aetiological 
factors to be reckoned with, in accounting for the chronic- 
ity of the rheumatic stage of purin excess, is not altogether 
the ingestion of raw material from which uric acid is 
formed, but also (and to no inconsiderable degree) the 
ingestion of too much nitrogenous food (both animal and 
vegetable) as well as all other food-essentials. In short, 
our patients are inclined to overeat and do overeat. 

In fixing upon a regimen for any given case, the 
quantity allowed will depend to some extent on the pre- 
vious habits of the patient in that respect. If always a 
heavy eater, he may require for a time more than the 
average individual but less than he has been accustomed to. 

The proportion of nitrogenous food, essential to the 
needs of the organism, will be greater in the case of the 
individual who uses up muscular energy, than he who 
expends brain force but, in nine cases out of ten, the 
laboring man greatly exceeds physiologic requirements, as 
does his sedentary neighbor. 



\ 

DIETETICS. 241 

From the animal kingdom, milk and eggs furnish 
abundant nitrogen and are purin free. The man of brawn 
will probably demand his meat, and with good reason; 
but he may be instructed in the manner of cooking it, so 
that the unbound purins will be removed. He should be 
made to understand that the glandular meats and meat 
extracts furnish little or no nutriment, but on the contrary 
are exceedingly rich in both bound and unbound purins. 
In short, the patient should have it fully explained to him 
why certain materials are not foods at all: that they only 
serve to aggravate his condition. 

Many sedentary patients require only a relatively 
small proportion of animal food and, even such as should 
be considered essential in a given case, may be either purin- 
free (as milk and eggs), or cooked in such manner (boiled) 
as to be comparatively free of unbound purins. 

In any instance, where a radical change in the diet be 
considered advisable, the change should be madegradually: 
introducing the new articles of food after some lapse of 
time, without producing" digestive disturbances. Further- 
more, it must be understood that no food substance of 
whatsoever nature be allowed, which the patient has learned 
from past experience is likely to disagree. Peas, beans 
and lentils, when ripe or dried, likewise peanuts and mush- 
rooms, are some of the articles that ought to be prohib- 
ited, not only because of the purin raw material which 
they contain but because of their indigestibility . Meat soups 
of all kinds, being strong solutions of uric acid (xanthins), 
should be absolutely forbidden. Adult meat is preferable 
to young meat (veal, etc.), and should be boiled or roasted 
— never fried. Fish, poultry and game birds are better 
than butcher's meat. 



242 URIC ACID AND ITS CONGENERS. 

Gouty Stage. — In this, the third and last stage of 
purin excess, although the dietetic treatment resembles in 
a general way that which has already been suggested, yet, 
in one important particular, the gouty individual must be 
much more careful, and that is in regard to the restriction 
of such food-material as tends to add to the dialyzing 
work of the kidneys — especially the epithelial cells lining 
the renal tubules. 

The many attempts to rid the system of purin waste 
(most of it needlessly introduced) have been so long and so 
oft repeated, that the epithelium of the renal tubules (by 
means of which such waste is dialyzed) has finally become 
injured, so that not only are nitrogenous molecules in the 
intermediately oxidized form of uric acid, imperfectly ex- 
creted, but also nitrogenous molecules in the completely 
oxidized form of urea. 

In those cases, which we recognize as "gout," 
"Bright's disease," "renal colic," "calculi," etc., the 
kidneys have become not only incapable of excreting an 
excess of uric acid or of urea, but incapable of excreting a 
normal quantity of each — -i. e., that resulting from tissue 
catabolism. The constant overwork forced upon the dial- 
yzing cells of the tubular epithelium has resulted in weak- 
ening them to a degree that even an average amount of 
work is illy performed so that eventually urea itself, as 
well as uric acid is retained. 

It is evident that the kidneys, in these cases, will have 
enough to do in eliminating (by aid of our medicinal 
treatment) the nitrogenous waste already retained in the 
system, without having their work increased by adding 
nitrogen from without. In short, the dietary of gout, es- 
pecially in the advanced stages, should consist of as little 



DIETETICS. 243 

nitrogen as is compatible with the health of that particular 
individual. 

Fried meat, meat and bean soups, glandular organs, 
foods and drinks that acidulate the blood, are absolute 
"poisons" in these cases. Inasmuch as the majority of 
these patients expend but little muscular energy, the pro- 
portion of nitrogen allowed in their dietary (during the 
eliminative treatment) should be cut down to at least one- 
fourth of the amount to which they have been accustomed. 
In fact, we believe that a strict dietary, like Haig's (but 
with less albumin), would prove advantageous in these 
particular cases. 

Evils of No-Flesh Diet. — -In an address, delivered 
Feb. 17, 1906, at the Harvard Medical School (Cf. St. Louis 
Med. Rev., March 10, 1906), BaronTakaki, Surgeon General 
of the Imperial Japanese Navy, shows very clearly that the 
dread disease "beri-beri," which has so long been a scourge 
to vegetarian peoples, is caused largely by errors of diet, 
especially to the lack of a proper proportion of flesh food. 

In 1884, a new regulation was issued by the Japanese 
Medical Corps, which allotted to the men of the navy a con- 
siderable increase in bread and meat ration. Previously to 
this time, they received thirty-six ounces of rice and only five 
ounces of meat or fowl daily. Under the new regulation, a 
twelve ounce meat ration is allowed. The death rate of 
beri-beri per thousand used to be very heavy; whereas, now, 
there have been only three cases in the last five years in the 
navy. This disappearance of beri-beri has been accom- 
panied with the disappearance also of certain intestinal 
diseases from which they used to suffer. 

" Before the new diet was established," says Baron 
Takaki, "the men of the Japanese navy could not stand the 
winters. Now they are able to stand them as well as the men 



244 URIC ACID AND ITS CONGENERS. 

of any other nation. In addition to the usual supply of rice 
the men now are given barley, a food which they did not have 
before; as well as more meat. The ration is rice, twenty- 
four ounces; barley, eight ounces; and meat, one pound, 
in the navy. The army tried the experiment of giving more 
meat and no barley; but comparative observations showed 
that the death rate was not lowered under this treatment." 

From these experiences, above reported, we learn 
something of the value of a mixed diet for men engaged in 
active pursuits. Not only is an average quantity of flesh 
food indicated, but vegetable proteid in more than one form 
or combination. The original ration of rice alone (with in- 
sufficient flesh allowance) furnished 1152 grains vegetable 
proteid while the new ration of rice and barley furnished 
but little more — 1224 grains. We judge, therefore, that it 
is not so much the increased quantity of proteid that is bene- 
ficial, as the different form in which it occurs. Further- 
more, the increased amount of vegetable proteid in the 
new diet requires but thirty-two ounces of vegetable food, 
whereas thirty-four ounces were ingested before. In short, 
it is decreased quantity plus improved quality of the food 
that has proved beneficial. 

It will be seen that a no-flesh diet is contraindicated 
under normal conditions; yet, of course, it may be resorted 
to temporarily in certain diseased conditions, more espec- 
ially in the gouty stage of purin excess where the work of the 
kidneys, in dialyzing nitrogenous waste molecules, should 
be rendered as easy as possible. Indeed, in these cases, a 
no-proteid diet is indicated, temporarily; for the kidneys 
should be given no additional nitrogenous work to perform 
during the interval in which we are attempting to aid the 
system in eliminating stored-up nitrogen by way of the 
various channels of exit. 



CHAPTER XXVII. 



ETIOLOGICAL THERAPY. 



Definition. — Though the mere coupling of the two 
words is, probably, in itself, enough to suggest the meaning 
of the term, "^Etiological Therapy," nevertheless, it is so 
essential to our purpose that there should be an intelligent 
comprehension of the idea we wish to convey by thus using 
the expression, that we have taken the liberty of coining a 
special definition of our own; to wit: 

As therapy means "the treatment of disease," and 
aetiology, "ascertainment of the cause," then the term "iEtio- 
logical Therapy," may well be defined as Treatment of 
Disease by Removal of the Cause; or, at least, by ascertain- 
ing the cause and attempting to remove it. 

Exciting ^Etiological Factor. — In the preceding 
pages, it has been shown that the symptoms and physical 
signs of the various disturbances, classed under the general 
head of "Purin Excess," are due to a common cause — i. e., 
the presence, at some point in the circulation or tissues, of 
an excess of nitrogenous uratic waste in either amorphous 
or crystalline form. 

We have seen that, floating in the blood-current 
throughout the vascular system, the urates in the arterioles 
are intermixed with colloid food-material, and in the ven- 
ules with colloid tissue-detritus, tending in this way to ob- 
struct the capillary flow — as in the "uricacidaemic" stage; 
and, whenever the reaction of the blood at such points of 
obstruction becomes suddenly lowered, from exposure of 
the part to influences of cold, absorption of acid material, 



246 URIC ACID AND ITS CONGENERS. 

or from muscular activity, the urates are precipitated out of 
solution and deposited in the adjacent tissue-structures — 
as in the "rheumatic" stage; and, if such deposition, oft 
repeated, takes place in the poorly oxygenated distal small 
joints, subject to strain, pressure, and sudden dealkaliza- 
tions of the surrounding synovia, crystallization occurs and 
concretions are formed — as in the "gouty" stage. In each 
case, it is obvious that the subjective symptoms may be 
traced directly and ascribed almost entirely to the mechani- 
cal irritation or interference of a mass of urates, either in 
the way of pressure against nerve-tissue or by preventing 
ingress or egress of blood by way of the capillaries; though, 
of course, it may be said, that the nerve-disturbance and 
metabolic-inactivity could possibly be due in part to some 
chemical action, such as may be produced by ammonia, 
which is known to be liberated during the process of purin 
catabolism. 

The objective signs, such as discoloration of the skin 
and conjunctivae, or a scant, high-colored urine, etc., are 
due to the same mechanical factor which, by impeding the 
capillary flow, restrains glandular action (especially of liver 
and kidneys), and consequently the blood and urine con- 
tain subcatabolized products and pigments which cause 
discoloration. In short, it will be seen that the exciting 
aetiological factor, in all of the abnormal conditions we are 
considering, is the presence of an excess of nitrogenous 
waste in the form of urates — usually "stationary at some 
point. 

From all this, it is manifest that one of the first require- 
ments of our "^Etiological Therapy" is to institute such 
measures as will best succeed in freeing the blood and 
tissues, at any point or points, of uratic excess, whether in 



^ETIOLOGICAL THERAPY. 247 

the colloid state or in crystalline form; and to remove it 
from the body entirely. 

But that is not all; for such removal is effective for 
only the time being. The same condition of affairs 
(presence of uratic excess) may be repeated, unless, in 
addition, some more radical means are taken to prevent. 
In other words, it is necessary to ascertain the predisposing 
causes and attempt their removal also. 

Predisposing ^Etiological Factors — Any agency 
of whatsoever nature, to whose direct or remote influence 
the presence of an excess of urates can be shown to be due, 
may properly be considered a "predisposing aetiological 
factor" in the cases under discussion. For instance, 
overeating leads to the introduction into the blood- 
stream of more chylous nutriment than can be utilized by 
the tissues, so that the returning capillaries contain over- 
plus fuel in addition to the normal uratic waste, which, 
together, may choke the flow, the uratic portion being 
likely to become precipitated; that is, by "stoking up" the 
human furnace with more fuel than can be burned, we are 
likely to "bank the fire," especially if the grate is allowed 
to become choked with the ashes and clinkers of uratic 
combustion. 

Persistent neglect in giving heed to Nature's notifi- 
cation, that the fecal reservoir is full and needs attention, 
often leads indirectly to the production of urates in excess 
and their deposition at some point. The retained fecal 
mass is constantly losing by osmosis much of the absorb- 
able portion that would otherwise be excreted with the 
egesta. This absorbed material not only acidulates the 
blood, lowering its reaction and tending to cause precipi- 
tation of the urates; but it must, of course, be eliminated 



248 URIC ACID AND ITS CONGENERS. 

chiefly by way of the kidneys, increasing the amount of 
work performed by the renal epithelium, which work, 
being of an unusual character, may injure the delicate cells 
in their dialyzing capacity and eventually cause retention 
of the urates. The liver, too, is burdened with the ad- 
ditional duty of metabolizing this absorbed material into 
forms less toxic, and may itself become injured in the work, 
eventually losing the power to oxidize into urea its normal 
proportion (50 per cent.) of uric acid, thus leaving the 
latter in excess in the circulation. Again, owing to the 
pressure of the distended colon against the iliac veins, the 
return venous flow of the lower extremities is partially 
checked, thereby causing stasis favorable to the deposition 
of urates in those parts. It will be seen, therefore, that 
constipation is one of the important "predisposing 
aetiological factors" which must be taken into account, if 
our aetiological therapy is to prove successful. 

It is not alone the "errors of omission" (such as 
neglect to keep open the sewers) that may serve to injure 
the liver and kidneys in this way; but also "errors of com- 
mission." For instance, the introduction of certain sub- 
stances into the system by way of food, drink, or drugs, 
may lead to the evil consequences we wish to avert. Over- 
plus food material, useless food material (especially the 
purins), certain beverages (as coffee, alcohol, acid drinks, 
etc.), and many toxic drugs (morphine, coal-tar antipy- 
retics and analgesics, etc.), may eventually so cripple the 
hepatic and renal functions, that increased uric acid pro- 
duction added to deficient uric acid elimination gives rise 
to an accumulation of urates in the system sufficient in 
amount to produce serious consequences. In fact, the 
"gouty" stage itself, may be reached, through these in- 



^ETIOLOGICAL THERAPY. 240 

dulgences or "errors of commission, " in a very short 
period of time. Alcoholic excess, in conjunction with the 
"purin-eating" habit, is probably one of the most common 
exciting causes of hepatic and renal insufficiency, which in 
turn are predisposing aetiological factors to be reckoned 
with in our aetiological therapy. 

From what has been said, it will be seen that three of 
the predisposing causes to be removed in the treatment of 
purin excess, are overeating, constipation, and hepatic- 
renal insufficiency. As overeating and constipation, how- 
ever, are themselves often responsible for the faulty action 
of liver and kidneys, it would, perhaps, be more practicable 
to limit our therapeutic study to the consideration of such 
measures as will succeed best in restoring the normal 
function of liver, kidneys and bowels, or, at least, aid them 
in the performance of such natural function. 

iNCiDENTALiETiOLOGiCAL Factors. — Under this head, 
we mean to include such causative agencies as are likely 
to be operative only at occasional intervals, produc- 
ing effects which are usually sudden and transient in char- 
acter: that is, effects which are more or less immediate, 
and in which the causes themselves suddenly disappear. 

In these cases, the aetiological factor being already 
withdrawn at the time the patient presents himself for 
relief, we cannot, of course, remove it as in the other 
instances described: we can only treat the effects and 
caution the patient to hereafter avoid exposure to like 
influences. 

Under this class of "incidental aetiological factors/' 
we may mention here two or three of those which are 
thought to be the most common, and with which it would 
be well for the physician to make his "purin excess" 



250 URIC ACID AND ITS CONGENERS. 

patients thoroughly acquainted; to wit: (i) Exposure of 
a part or of the entire surface of the body to cold, or to cold 
and dampness combined; (2) Violent or unusual mus- 
cular efforts; (3) Holding the body or one of its mem- 
bers in a constrained or awkward position or attitude 
for some time, causing pressure upon the veins at some 
point, thus serving to prevent the return venous flow below, 
which is likely to result in capillary stasis or obstruction,, 
and uratic deposition — as when sitting in the well-known 
"cross-legged" position. 

In the particular instance last mentioned, the evil con- 
sequences are likely to be precipitation of the urates into 
the gastrocnemii of the calf, producing night cramps of the 
foot or leg, or, possibly, initiating an attack of podagra. 

Summary. — In summing up the subject, it will be seen 
that our "aetiological therapy" may be conveniently 
grouped or studied under three principal headings; viz.: 

1. The use of effective medicinal or other means to 
remove from the circulation or tissues the exciting aetio- 
logical factor itself. 

2. The adoption of such measures, hygienic, dietetic 
and therapeutic, as will tend to prevent or relieve the evil 
influences of predisposing aetiological factors, especially in 
the way of aiding or restoring the normal function of liver,, 
kidneys and bowels. 

3. To caution against exposure to certain incidental 
aetiological factors, at the same time treating symptomati- 
cally the ill effects already produced by them. 



CHAPTER XXVIII. 

CURRENT THERAPEUTIC METHODS. 

Nosological Basis. — Before studying, in its clinical 
details, the treatment of purin excess based on a rational 
"aetiological therapy," as briefly outlined in the last 
chapter, we will first consider the methods now in vogue, 
based on an entirely different and irrational nosological 
therapy. 

Our medical nomenclature is altogether an arbitrary 
affair, such a scheme of name-grouping or classification 
being resorted to, not only in pathology, but in botany, 
chemistry, and other sciences, for convenience of study. 
But this simple fact has long been lost sight of and it is now 
the custom to treat the names of disease rather than the 
abnormal condition itself. That is to say, our text-books 
recommend a certain line of treatment for all disorders 
bearing the same name, notwithstanding that they may be 
and possibly are, in many instances, due to quite different 
aetiological factors, which are still in active operation, and 
instrumental in keeping up the chronicity of the given 
trouble. Or again, and what is much worse, we turn to 
volume one, two, or three, of any system of medical prac- 
tice, which volume may be devoted especially, for instance, 
to diseases of the respiratory tract, and there find grouped 
under their respective headings, such disease-names as, 
"chronic nasal catarrh," "chronic bronchitis," "bronchial 
asthma," "hay fever," etc., with a similar treatment rec- 
ommended for all of the same name, but a different treat- 
ment for those of different names, notwithstanding the fact 



252 URIC ACID AND ITS CONGENERS. 

that the latter (though differently named according to the 
anatomical character and locale of the tissues affected) 
may be due to precisely the same cause, which is still 
present and in active operation. 

In short, the arbitrary method of classifying and 
naming diseases according to the anatomical tissues 
affected, has led to the irrational plan of treating alike 
those diseases bearing the same name, while those of unlike 
names are differently treated. For example, we are taught 
to treat bronchial asthma along certain definite lines, and 
lumbago along certain other definite lines. Because 
differently named, they are considered to be two distinct 
and separate diseases, requiring different medicinal treat- 
ment. But it should be understood at the outstart, that 
it is not the name that ought to decide the line of treatment. 
We know, that, oftentimes, the same medicinal treatment 
will prove effective in both bronchial asthma and muscular 
rheumatism (notwithstanding their different names) since 
they are frequently due to a common aetiological factor — a 
factor which may be removed in both cases by the same 
effective medicinal means. 

A Source of Therapeutic Error. — If diseases bear- 
ing different names were always, or even generally, caused 
by different aetiological factors, no great harm would arise 
from the fact that different lines of medicinal treatment are 
recommended in our current text-books in such cases; 
but, as a matter of truth, widely different tissues from an 
anatomical as well as histological standpoint are subjected to 
the same systemic aetiological factor, and the same internal 
treatment will be required to remove that irritant factor 
(mechanical or chemical) and effect a cure of the diseased 
condition in each case. For illustration, the tissues of the 



CURRENT THERAPEUTIC METHODS. 253 

phalangeal joints of the metacarpus or metatarsus, as well 
as the tissues of the glandular organs will both be affected 
in their peculiar way whenever the circulation is impeded 
at either point, thus interfering with the supply of nutrition 
and removal of waste. The treatment should be the same 
(i. e., eliminative) in both cases, notwithstanding the widely 
different character and locality of the tissues involved and 
the different disease-names usually applied. Under the 
irrational plan of therapy now in vogue, no one would 
think of treating a disorder of the finger or toe joints by the 
same medicinal means as used in the case of the glandular 
organs. And yet, we know that the "gouty" toe joint and 
"gouty" liver or kidney often go hand in hand. 

Symptom Therapy. — There must, of course, be some 
definite plan or system observed in the naming of disease 
and, while our present system is not the best, it has become 
thoroughly established and doubtless will remain for many 
years to come. But it must not be forgotten that the 
disease-titles now in use, are simply descriptive of the 
principal symptoms or of some physical aspect presented. 
In fact, the name represents or portrays the outward effects 
or manifestations of the disease rather than its inherent 
nature or causation. For instance, such signs as heat, 
swelling, color and pain (inflammation) suggested the 
adoption of the Greek termination itis, added to the 
anatomical name of the tissue thus affected, as in the terms, 
"bronchitis," "peritonitis," "tonsillitis," "cellulitis," 
"pleuritis," "pneumonitis," "urethritis," "meningitis," 
"otitis," "pharyngitis," "appendicitis," "nephritis," etc., 
etc. Sometimes the Latin term was used instead, as in 
pneumonia, diphtheria, hysteria, etc. Again, the Latin 
suffix, meaning "to flow," was added to the word-root 



'254 URIC ACID AND ITS CONGENERS. 

indicating whether the flow was checked or increased, as 
amenorrhea, leucorrhea, otorrhea, etc. In case of pain, a 
similar term was used to suggest that symptom, as 
neuralgia (nerve pain) myalgia (muscle pain), odontalgia 
(tooth-pain), etc. The word "fever" is often added to 
some physical characteristic of the complaint, as scarlet 
fever, typhoid fever, malarial fever, spotted fever, etc. 
Again, a descriptive term of some physical peculiarity of 
the disease is adopted, as smallpox, measles, chickenpox, 
whooping cough, croup, etc. 

It will be seen that in recommending the same treat- 
ment for diseases of the same name, our text-books 
are simply teaching us to treat similar symptoms alike. 
We know that this is unscientific, for the same symptoms 
are oftentimes quite differently caused and require different 
medicinal treatment to remove such cause. It is not the 
effect, but the cause that demands our chief attention, if we 
expect to attain a complete cure and afford permanent 
relief. 

We know, for example, that the symptom, "inflam- 
mation," which is the one most commonly adopted in 
naming diseases under our present system, may be caused 
by a hundred different irritant factors, and it is unreason- 
able to expect that these different etiological factors can all 
be removed by the same medical treatment. Or, on the 
other hand, many different symptoms may be caused by 
the same irritant factor, the symptomatic evidence depend- 
ing on the anatomic character and location of the par- 
ticular tissue involved. For instance, an obstruction of the 
blood-current may cause headache, or insomnia, or both, 
when occurring in the cerebral capillaries; leg or foot 
cramps, if in the vessels of the lower extremity; "bilious- 



CURRENT THERAPEUTIC METHODS. 255 

ness," if in the hepatic or portal vessels; hemorrhoids, if in 
the rectal veins; scanty urine, if in the renal vessels, and 
so on. According to our modern nosological or sympto- 
matic therapy, these different manifestations would call for 
quite different medicinal treatment; but, according to the 
rational aetiological therapy, suggested in our previous 
chapter, the same medicinal measures should be employed 
in each instance, i.e., when due to a common cause. 

In the "uricacidaemic" stage of purin excess, we have 
such different disease-names or symptoms, as migraine, 
neurasthenia, hypochondria, insomnia, coryza, anaemia, 
odontalgia, neuralgia, etc. According to the present plan 
of therapy, these conditions are treated differently; but, if 
our plan of "aetiological therapy," as suggested in the last 
chapter, be followed out, they will oftener than not be 
treated alike. Under the old regime, when fever and 
pain are prominent symptoms, analgesics or antipy- 
retics are given; for anaemia, a tonic; for insomnia, an 
hypnotic; for neurasthenia, hysteria or hypochondria, a 
sedative; for coryza, an antipyretic, analgesic, antiphlo- 
gistic or alterative, either singly or combined. Such treat- 
ment relieves temporarily, simply because it masks or 
neutralizes the symptoms. The cause itself is allowed to 
remain. 

In the "rheumatic" stage, we have scores of differ- 
ently named diseases, according to the locality affected and 
the predominence of one or more signs, as arthritis, myal- 
gia, lumbago, sciatica, bronchitis, tonsillitis, etc. But, as 
may be seen, these are only symptomatic titles, given 
according to the locality and anatomic character of the 
tissues affected. Under our "aetiological therapy," w hen 
similarly caused they would all be treated substantially 



25 6 URIC ACID AND ITS CONGENERS. 

alike, so far as internal medication is concerned. Though 
the symptoms of the rheumatic stage may vary, therefore, 
according to the histologic nature of the tissue-structures 
where the precipitate occurs, thus leading to different 
manifestations and their corresponding different disease- 
titles, yet the aetiologic factor itself (i. e., the uratic deposit) 
is practically the same and calls for the same solvent or 
eliminant measures to effect its removal from the given 
location. This does not mean that the eliminant agent is 
used in the sense of a "cure all," for, on the contrary, it is 
indicated only for a single purpose. Notwithstanding the 
various manifestations that are made to disappear, only a 
single cause is removed. 

Again, in the last, or "gouty" stage, we are confronted 
with such symptomatic disease-titles, as podagra, rheu- 
matoid arthritis or arthritis deformans, endarteritis, 
atheromata, nephritis or Bright's disease, renal colic, 
calculi, etc. As in the previous stages, a rational aetiologi- 
cal therapy in these cases, calls for a similar line of treat- 
ment. In short, we should not permit the arbitrary 
naming or classification of diseases now in vogue (based 
on the physical effects produced) to blind us to the fact 
that the masking or neutralizing of such effect, does not, 
by any means, remove the cause and cure the complaint. 

Its Limitations. — It is not meant to convey the 
impression here that we consider the present symptomatic 
therapy to be entirely useless or futile. On the contrary, 
we think that it is very often advantageous to mask or 
neutralize acute symptoms, especially those of a painful 
character. But this is only for a temporary purpose. 
Immediate relief is demanded in certain cases, and we 
administer the sedative, hypnotic, analgesic, etc., to afford 



CURRENT THERAPEUTIC METHODS. 257 

such instant relief; but our curative measures aim to 
eliminate the cause, and when this object is attained the 
"effects" will often take care of themselves. Of course, 
in many conditions, as in "inflammation," we direct at- 
tention to the local (anatomical) trouble and endeavor to 
ameliorate the particular symptoms of the same; but, at 
the same time, we should not forget to look for the irritant 
factor which is responsible for the given inflammation, and 
adopt such means as will tend to remove it from the 
system. 



CHAPTER XXIX. 

EFFECT OF REMEDIES IN COMMON USE. 

A Frequent Indication. — Among the many symp- 
toms, effects, manifestations, or so-called " diseases, " 
which may properly be classed under the head of purin 
excess, those of the first or uricacidaemic stage are probably 
the most commonly met with in general practice and most 
frequently require prompt medicinal aid. The majority of 
such cases are of a subacute character, in which the 
partially precipitated amorphous urates in the colloidal or 
so-called " Kugelurate" form, choke the capillaries at one 
or more points and give rise to the customary glandular 
insufficiency due to an impeded circulation, and to the 
various local disturbances caused by pressure of the dis- 
tended vessels. 

If the absorbability of a given mass of these amor- 
phous urates is such that it can be taken up in the circu- 
lation and removed elsewhere, as indicated by the fitful 
and transitory character of the pains, occurring first at one 
point and then at another, we have pretty good evidence 
that our "^etiological therapy," if adopted, will prove 
successful; that is, it would seem that by slightly increasing 
the alkalinity and consequent solubility of the blood, the 
latter would be enabled to hold the urates in solution long 
enough to reach the kidneys, from whence they would be 
eliminated from the body entirely. 

Prevailing Custom. — But, instead of directing at- 
tention to the elimination of these threatened deposits, the 
general practice is to prescribe some effective agent to 



EFFECT OF REMEDIES IN COMMON USE. 259 

ameliorate the symptoms which they produce. In other 
words, something is given to relieve the subjective sen- 
sations complained of. If the most troublesome mani- 
festation should chance to be a headache, toothache, 
mental and physical inertia, or wandering pains, accom- 
panied possibly with a slightly rising temperature, the 
patient is almost invariably given an antipyretic or anal- 
gesic medicine — usually one of the coal tar products. 
Antifebrin, phenacetin, morphin, quinin, and remedies 
of this class are the favorites, the object being to afford 
immediate relief. 

The patient generally appears satisfied with this 
make-shift mode of treatment, until constantly recurring 
attacks or exacerbations point out to him the necessity of 
having more radical measures employed, for which pur- 
pose he is forced to seek other professional advice. In 
ninety per cent, of such cases, however, the new attendant 
pursues a like plan of symptomatic treatment, and the 
primary disorder either becomes stubbornly chronic, or the 
rheumatic stage is speedily reached. 

Temporary Effects. — Though the drugs above 
mentioned will probably produce satisfactory results so far 
as the immediate neutralization of the symptoms is con- 
cerned, nevertheless their effect is but temporary. This 
cannot well be otherwise, for all of these agents are pre- 
cipitants. They tend to further acidulate the blood 
(already subalkaline), causing the urates and other waste 
salts to be thrown down as a precipitate and deposited in 
the tissues, thus freeing the circulation, increasing gland- 
ular and cellular activity for a time, relieving the capillary 
stasis and consequent pressure and pain. In short, the 
urates are simply precipitated out of solution into the sur- 



260 URIC ACID AND ITS CONGENERS. 

rounding connective-tissue structures and, as soon as the 
remedy is withheld and the blood regains its former degree 
of reaction and lessened viscosity, the deposits are re- 
absorbed into the circulation where they may again serve 
to impede the capillary flow and reproduce all of the 
previous effects due to such impediment. 

These precipitant remedies, as will be seen, produce 
almost immediate relief of the symptoms owing to the 
temporary removal of the urates out of the capillaries into 
the tissues, which permits the ready flow of blood to the 
glandular organs and other parts — i. e., so long as such 
obstruction remains absent. But the causative factor is not 
removed from the system; it is still present and will be 
heard from again as soon as the effect of the remedy is 
gone. Furthermore, by driving the deposits in this way 
into the tissues, a rheumatic attack may be initiated, as is 
sometimes seen when prescribing an analgesic or antipy- 
retic drug for the relief of headache, vague pains, a 
threatened corvza, eczema, etc. 

III Effects. — Inasmuch as these patients are already 
suffering from the effects of acidosis (i. e., decreased alka- 
lescence of the blood and extra vascular fluids) it is evi- 
dently irrational and unscientific to increase such acidosis 
by introducing precipitant remedies into the system. The 
urine in these cases is scant, high-colored and overacid, 
which would seem to point out the necessity of an alkaline 
remedy rather than an acid remedy. The effect of these 
latter drugs in acidulating the blood is practically the same 
as that produced by uric acid itself, which is known to 
temporarily relieve the symptoms by causing precipitation 
of the retained urates. The evil hour is simply postponed 
and the danger from accumulation constantly increases. 



EFFECT OF REMEDIES IN COMMON USE. 201 

It is like the stimulating effect of opium on the habitue, 
who craves more of the poison to relieve the ill effects 
already produced by the drug. In both instances, the 
action is cumulative. 

For the temporary relief of insomnia, sulphonal or 
some similar agent is given; but the therapeutic action in 
this case is like that of the analgesic in relieving headache. 
The pressure from the distended cerebral vessels is relieved 
momentarily by driving the uratic obstruction into the 
tissues. On the following night, however, the same tactics 
must be repeated, and so on indefinitely. The aetiological 
factor is not removed from the system. Furthermore, 
repeated doses of sulphonal are known to interfere with the 
oxidizing function of the liver, i. e., less than the normal 
proportion (50 per cent.) of uric acid is transformed into 
urea. The inevitable result is an increased amount of uric 
acid left in circulation, which tends further to obstruct the 
capillaries and aggravate the insomnia. If the latter dis- 
order be due to an obstruction of the cerebral capillaries 
it is evident that a cure will not be effected until such 
obstruction is entirely removed from the system. 

If it be granted that cellular inactivity or glandular 
insufficiency and faulty metabolism, accompanied with 
depression of spirits, languor, vague pains, malaise, etc., 
be due in a given case to retention of nitrogenous waste, 
which accumulates at some point in the capillaries and 
impedes the circulation there, very little argument would 
seem to be required to convince the practitioner of the 
folly of prescribing any drug that tends in the least to 
prevent the elimination of such waste by the natural 
channels of exit. It is fully as essential to the burning 
organism that the ashes and clinkers of combustion be 



262 URIC ACID AND ITS CONGENERS. 

removed as that a sufficient amount of the proper kind of 
fuel be introduced. Waste and repair go hand in hand, 
and it is certainly a mistaken therapy on the part of the 
physician to oppose Nature's efforts to remove such waste. 
But the precipitant remedy does just this in the cases we 
are considering, for it has been convincingly shown by 
clinical experiment that antipyretic and analgesic drugs 
acidulate the blood and urine and check the elimination of 
uratic waste. 

Action of Drugs Used in Rheumatic Stage. — For 
the relief of the symptoms resulting from the irritating 
presence of deposits in the tissues or joints, many different 
drugs are employed, varying according to the histologic 
nature of the tissues involved and their anatomical 
position. If the mucous membranes chance to be the seat 
of the deposits, as in bronchial asthma, hay fever, tonsil- 
litis, etc., local applications are, of course, indicated in 
many instances to remedy the ill effects of congestion or 
inflammation; and, during the acute attacks, as in spas- 
modic asthma, to relieve the dyspnoea, inhalation of such 
volatile substances as nitrite of amyl, or the fumes from 
burning stramonium leaves or nitre paper may be em- 
ployed. This form of treatment is essential to tide over an 
existing attack by influencing, through direct means, the 
dilation of the surface arterioles, thus permitting the 
temporary passage of the urates to the deeper and larger 
vessels; while, between attacks, such curative agents as 
hydriodic acid, iodide of potash and other well-known 
alteratives are generally used. 

The latter remedies are rationally indicated and pro- 
duce good results in these cases, -provided the exciting 
aetiological factor (the deposit) is alone responsible for the 



EFFECT OF REMEDIES IN COMMON USE. 263 

given manifestation. But, in the majority of instances, 
predisposing causes, such as hepatic insufficiency and con- 
stipation are responsible for the oft-recurring attacks, and 
it is impossible to effect a cure so long as these disturbing 
factors remain, which are not removed by the iodide treat- 
ment. Notwithstanding the fact, therefore, that potassium 
iodide is known to lessen the viscosity of the blood and 
decrease acidosis, thereby aiding in the solution of the 
urates and their probable resorption into the circulation, 
the patient remains liable to further attacks, until the 
proper means are taken to restore the natural functions of 
liver and bowels and prevent the continued accumulation 
of urates from faulty oxidation and elimination. 

Effects of Salicylates. — In rheumatism proper, 
especially articular rheumatism, the salicylic acid prepar- 
ations have been used most extensively in recent years. It 
has been shown by laboratory experiment as well as by 
clinical investigation that the initial doses of salicylic acid 
increase the excretion of urates. This increased urinary 
excretion is attributed by different authors to different 
causes. In the opinion of Weidner, Levison, and others, 
the acid simply increases the number of leucocytes, the 
increased excretion of urates being the result of the in- 
creased leucocytosis. Haig and others believe, on the 
contrary, that the drug acts like the alkalies, and "flushes 
out" the uric acid. The question is still a moot one. 

Whatever the precise nature of this observed action 
on the part of the salicylates, we know that the urgent 
symptoms of articular rheumatism are ameliorated by thus 
increasing temporarily the excretion of urates. In cases of 
this description, where treatment is only given for a few 
hours to relieve acute manifestations, the therapeutic effect 



264 URIC ACID AND ITS CONGENERS. 

of the salicylates is usually satisfactory. But if more pro- 
longed medication is indicated, this remedy will prove a 
failure. Its deleterious action on the stomach, and, later, 
on the kidneys, tends to prevent the free elimination of 
urates, and its continued administration proves harmful. 

In cases of so-called "muscular rheumatism," chronic 
arthritis, sciatica, lumbago, etc., the transient effect of the 
salicylates, in increasing uratic excretion, falls short of the 
true therapeutic requirements. Not only is it necessary in 
these instances to neutralize acidosis and effect the re- 
sorption and removal of the local deposits bv more pro- 
longed treatment; but, like the cases of bronchial asthma, 
hay fever, etc., already described, it is essential that some 
effective means be taken to insure oxidation of purin waste 
and prevent further accumulation, by stimulating and 
aiding the function of liver, kidneys and bowels. 

Concerning the Alkalies.— The salts of the alkali 
metals, sodium, potassium, lithium, etc., have proved 
beneficial in the treatment of both the uricacidaemic and 
the rheumatic stage of purin excess. From chemical urin- 
alysis, we know that these agents, when introduced into 
the system, can be made to neutralize the acidity of the 
urine — changing the reaction to alkaline in some instances. 
This certainly ought to convince the most skeptical that 
the alkalescence of the blood is raised at the same time. 
But, owing to certain titration experiments with solutions 
(in vitro) analogous in character to the blood, the pure 
chemist says otherwise. According to the theoretical- 
experimental deductions of the laboratory expert, the 
alkalinity of the blood is not affected by the introduction 
of alkalies. It would seem that nothing will neutralize the 
acidosis, in these cases, according to the pessimistic views 



EFFECT OF REMEDIES IN COMMON USE. 265 

of the professional chemist. Indeed, the latter has become 
a therapeutic nihilist. 

But the general practitioner knows that some of these 
alkaline agents will neutralize acidity. Clinicians of wide 
experience, such as Jacobi, have demonstrated to their 
satisfaction, that alkaline waters do possess solvent power 
over the urates to a limited extent. The amount of alkali, 
however, contained in the natural waters is too slight, 
according to this eminent authority, to produce much 
therapeutic effect. He believes that those artificially 
prepared are much to be preferred. The same objection 
holds against the majority of tablets and effervescent salts 
and mixtures; not enough alkali is absorbed into the blood 
to produce the solvent effect desired; i. e., too large doses 
are required to hold the urine at the neutral point a 
sufficient length of time. 



CHAPTER XXX. 



CONCERNING GOUT THERAPY. 



Status of the Ouestion. — In "The Practical Medi- 
cine Series of Year Books," for 1905, the author, Frank 
Billings, of Chicago, declares in his introductory note that 
his volume contains a review of the best literature of medi- 
cine for the year. Under the head of " Metabolic Diseases," 
gout occupies the first place, concerning the treatment of 
which we note the following: "The keynote to the treat- 
ment lies in (1) limiting all toxic influences and formation of 
toxins, particularly in the alimentary canal, in order to 
minimize the retrograde metamorphosis of the body nn- 
cleins, (2) in preventing the absorption of all toxic mater- 
ial, or (3) in promoting the elimination of the products of 



toxic agents. 



Immediatelv following the foregoing paragraph, in a 
parenthetic note commenting on the use of salicylates in the 
treatment of gout, the associate editor, Dr. j. H. Salisbury, 
of Chicago, a well-known writer on the uric acid problem, 
calls attention to the fact that the increase of uric acid ex- 
cretion seen after the administration of salicyl compounds 
may be due to the excitation of a digestive leucocytosis as 
shown by Schreiber and Zaudy. He says: "The action of 
these remedies on the kidney should be borne in mind, as the 
researches of Luthje have shown a direct injurious influence 
from doses similar to those used for therapeutic purposes. 
The long-continued use of such a remedy, in patients 
predisposed, as gouty patients are, to disease of the kidney, 
is not advisable." 



CONCERNING GOUT THERAPY. 267 

From the preceding two paragraphs, the reader gleans 
the substance of practically all that can be learned on gout 
therapy, from the most careful study of the published utter- 
ances of our modern authorities appearing in the various 
foreign and domestic journals and text-books issued during 
the past ten years. The tendency of modern scientists is to 
point out how little is positively known concerning the 
pathogenesis of gout, and at the same time to demonstrate 
the futility of attempting a cure by means of any known 
form of internal medication. 

It is claimed by a few laboratory experts that gouty 
concretions are unaffected by alkalies extra corpus, conse- 
quently the alkaline treatment must prove ineffective; but 
nothing better, or, rather, nothing at all, is suggested in 
its stead. The physician and his patient are left practi- 
cally helpless. 

Again, while fanciful theories galore have been offered 
concerning the relation of uric acid to gout, yet, from the 
therapeutic standpoint of the chemist, the anti-uric-acid 
regime is deemed inoperative. 

In his recent work on "Uric Acid," McCrudden in- 
dorses the opinion of Rosenfeld that alkalies have no in- 
fluence on the solvent power of the urine for uric acid; and 
furthermore, that the alkalescence of the blood is unaffected 
by drugs. Another laboratory experimenter (Joulie), goes 
so far as to claim the discovery of a new method of deter- 
mining the acidity of a given solution, which proves that the 
blood, instead of being alkaline as we have always been 
taught, is in reality neutral or acid, notwithstanding its 
reaction to litmus. To such extremities is the closet stu- 
dent brought by limiting his investigations to chemical 
findings in vitro. 



268 URIC ACID AND ITS CONGENERS. 

As a result of the conflicting views of the chemist and 
clinician, concerning the inherent nature of gout and the 
effect of medication, the existing literature on the subject 
we are discussing is very unsatisfactory. The majority of 
those other investigators, however, who have happily had 
experience along the lines of clinical observation as well as 
laboratory study — such well-known authors as Chittenden 
Futcher, Burmin, Pfeiffer, Aronsohn, von Noorden, Men- 
del, and others — are inclined to accept the original teachings 
of Garrod, as briefly alluded to in a previous chapter. 

It is now quite generally agreed by these authors, that 
the alkalescence of the blood is reduced in gout; that the 
circulation is overcharged with urates at the beginning of 
and a few days prior to the attacks; that the urine contains 
an excess of urates at the height of an attack and as it is 
passing off; that the gouty subject excretes exogenous 
purins but poorly; that the accumulation in the system is 
chiefly owing to retention, because of insufficient kidney 
elimination from disease of that organ; that the acute joint 
symptoms are probably due to variations in the reaction of 
the synovia (dealkalization followed by hyperalkalization) 
causing sudden dissolution of the previously inert crystal- 
line formations; that the alkaline eliminative treatment is 
theoretically, rationallv and experientially indicated. I 
am pleased to state at this point that clinical experience 
enables me to heartily indorse these latter views of the 
subject. 

Prevailing Type of Medication. — Most modern 
clinicians will doubtless acknowledge the force of the state- 
ment made by Billings, that the "keynote to the treatment" 
of the gouty stage of purin excess (as in the two previous 
stages) is to limit all toxic influences which tend in any way 



CONCERNING GOUT THERAPY. 269 

to inhibit the retrograde metamorphosis of the body nu- 
cleins, striving, at the same time, to prevent the absorption 
of toxic material and to promote the elimination of the pro- 
ducts of toxic agents, particularly from the alimentary 
canal. In short, the experience of the general practitioner 
has taught him the therapeutic value of drugs that stimulate 
the action of the organs of defense (especially the liver) and 
aid in cleaning out the intestinal tract, thus preventing the 
absorption or introduction into the circulation of such 
waste material as tends to acidulate the blood and extra- 
vascular fluids. Alkaline diuretics are also commonly pre- 
scribed to further elimination by way of the kidneys. 

Concerning the particular medicinal agents to be em- 
ployed for the foregoing purposes, authorities differ. Per- 
sonally, I have come to agree with Salisbury, Pfeiffer, and 
others, that the prolonged use of the salicylates is exceed- 
ingly detrimental. While they do increase the excretion of 
urates temporarily, and in acute cases may be employed 
two or three days for that purpose, (as in acute articular 
rheumatism) yet, as* the ultimate effect on stomach and 
kidneys is such as to lead to absolute injury and reten- 
tion, their administration in chronic cases or for prophy- 
lactic purposes is to be strongly condemned. 

The same objection holds against the use of the colchi- 
cum preparations. Continued ingestion of this drug in 
effective doses almost invariably causes congestion of the 
delicate epithelium of the renal tubules; and the patient, 
eventually, is done more harm than good. Moreover, 
neither of these two agents produces the effect on liver and 
bowels so much to be desired; nor do they possess that 
essential solvent power, to render them beneficial in cases of 
gravel and calculi. 



270 URIC ACID AND ITS CONGENERS. 

Use of Alkalies. — Notwithstanding the recently 
published statement of McCrudden (Cf. "Uric Acid," p. 
243) that the bulk of laboratory evidence, so far as he has 
examined into the matter, " seems to indicate that alkalies 
neither decrease nor increase the excretion of uric acid"; 
nevertheless, the bed-side evidence reported by the general 
practitioner must be taken as conclusive that the alkalies 
very often do increase such excretion — i. e., in cases in which 
excess actually exists in the blood, as in gout. Chemists, 
themselves, disagree on this point; but there is little doubt 
in the minds of physicians. 

Physicians do disagree, however, as to which is the 
most effective alkali to be employed. The most popular 
agents of this class are the salts of sodium, potassium and 
lithium. The bicarbonate of sodium, iodide of potassium 
and citrate of lithium have been perhaps most extensively 
used until within the past two years. When one of these 
agents is given in such form and in such considerable dosage 
as to "saturate" the system, it is known to produce effects 
which are desirable in a rational gout therapy; to wit: — 
1. To neutralize the urine. 2. To lessen the viscosity of 
the blood. 3. To increase temporarily the excretion of 
purin nitrogen. 4. To cause diuresis. 

Unfortunately, in practical therapeutics, it is very diffi- 
cult to insure the absorption of a sufficient quantity of the 
given alkali to produce the above effects. For example, four 
hundred grains of the bicarbonate salt, given daily, have been 
found necessary to hold the urine constantly at the alkaline 
point of reaction to litmus; consequently, in the pharma- 
ceutical form in which these alkalies are usually presented 
to us (tablets, effervescent salts, mineral waters, etc.), it is 
impracticable to administer them in adequate dosage. As 



CONCERNING GOUT THERAPY. 271 

ordinarily prescribed, not enough of the alkali becomes 
absorbed to produce but the most evanescent effects — cer- 
tainly not enough to insure the solution of gouty concre- 
tions. 

In the chemical combination in which the sodium salt 
is commonly administered, the greater portion passes 
through the intestinal canal and is expelled with the egesta in 
the form of sodium hydrogen sulphide, thus serving as a 
laxative. The phosphate of sodium is most frequently 
utilized for this purpose. If the alkali be given singly, 
therefore, in simple molecular combination (as a base with 
an acid), little effect is observed, so far as increasing the ex- 
cretion of urates is concerned. In fact, most of the absorba- 
ble portion is oxidized in the body to carbonate, which 
eventually adds to the crystallization of sodium acid urate. 

A similar effect is said to take place when a potassium 
or lithium salt is given singly, in the chemical combination 
of acid and base (though to a lesser extent in the case of 
lithium) ; they are transformed to carbonates after absorp- 
tion, and though at first a slight increase of uric acid excre- 
tion is observed, a decrease is afterward shown; but this, 
in some instances, is probably due to the fact that the origi- 
nal retention was slight, and the excess within the system has 
been eliminated. (Cf. C. Clar, in Centralblatt fur die Medicin 
Wissen, Vol. XXVI, 466.) 

It will thus be seen that, while the single salts of the 
alkali metals, as ordinarily prescribed, can hardly be ex- 
pected to remove the crystalline biurates from the system, 
nor cause dissolution of gouty tophi, they may and do pro- 
duce some beneficial effects, temporarily, by eliminating 
loose semi-crystalline ureids and serving, to a certain ex- 
tent, as a material aid to the normal excretory functions, by 



272 URIC ACID AND ITS CONGENERS. 

neutralizing the urine and increasing its flow, thereby 
enabling the latter to hold a greater quantity of purin waste 
salts in solution. 

Much greater therapeutic effects may, of course, be 
expected when the alkaline agent is ingested in such chemi- 
cal combination that the base may be absorbed and set free 
to unite with the uric acid, while the acid radical is taken 
up with some other base requiring elimination, both be- 
ing removed. 

Effect on Genito-urinary Concretions. — Though 
the simple alkaline salts, prescribed singly or in conjunc- 
tion with other simple alkaline salts, do not in the ordinary 
dosage become absorbed in sufficient amount or in such 
chemical form as to materially affect the dissolution of the 
crystalline formations in joints and other connective tissues 
within the body, as in the so-called " regular gout," they 
do neutralize the reaction of the urine to such an extent that 
the latter may hold the urates in more perfect solution or 
suspension, and in this way prevent the irritation of the 
genito-urinary mucous lining from the passage of small 
concretions or gravel. 

As remedies in cystitis, therefore, or for the purpose of 
allaying the kidney irritation due to the imperfect solution of 
minute irregular urate crystals, or gravel, the administra- 
tion of the simple alkaline salts has been found to produce 
fairly satisfactory results. For this purpose, the citrates 
have become quite popular, being especially indicated 
whenever the urine is concentrated and overacid. 

Laxative Effects. — Again, for their laxative effects, 
the alkaline cholagogues prove beneficial in the gouty stage. 
By initiating an increased flow of bile and by stimulating 
the action of the liver, these agents tend to prevent the ab- 



CONCERNING GOUT THERAPY. 273 

sorption of toxic material from the alimentary canal and 
promote the elimination of the products of toxic agents: 
two important therapeutic effects, which are essential to 
the "keynote of the treatment," as laid down in the recent 
works of Billings and others. 



CHAPTER XXXI. 

THE ALKALINE-ELIMINANT. 

Definition. — In its therapeutic application, the term 
" alkaline-eliminant," is used here to designate any remedial 
agent, that, prescribed in ordinary medicinal dosage, is 
known to alkalinize an overacid urine and aid in the elim- 
ination of urate salts in cases of purin excess. 

Its Clinical Purpose. — The main object in prescrib- 
ing a remedy of this character is to effect the removal from 
the system of the "exciting aetiological factor/' as described 
in our previous chapter on " ^Etiological Therapy." At the 
same time, if such remedy prove effective in causing the 
removal of the chief " Predisposing ^Etiological Factor," 
described in the aforementioned chapter, its therapeutic 
value would be enhanced tenfold. 

The action of the alkaline-eliminant in increasing the 
excretion of urates is to be observed, of course, only so long 
as an excess of uric acid remains in the blood or tissues, 
capable of being removed. When such excess has actually 
been removed, knowledge of the fact will be apparent from 
the disappearance of certain characteristic subjective and 
objective symptoms, and from the gradual decrease in the 
urinary excretion of urates observed, until, finally, the 
normal, or less than the normal per cent, is reached. 

Unlike the precipitant agent, — which reduces the 
amount of uric acid excreted to the normal, or lower, by 
driving the excess out of the circulation into the tissues — 
the alkaline-eliminant merely hastens the hour when the 
minimum excretion is reached, by stimulating the hepatic 



THE ALKALINE-ELIMINANT. 275 

function and aiding in the more complete oxidation of the 
purins (40 to 60 per cent.) to the end stage (urea), thereby 
decreasing the amount of uric acid left in circulation and 
lessening the total amount to be excreted. In other words, 
inasmuch as in uricacidaemic patients much of the excess of 
uratic waste in circulation is owing to the failure of the 
"torpid" liver to oxidize its due share (50 per cent.) of uric 
acid to urea, as in health, it is evident that when the hepatic 
function becomes more active as a result of the administra- 
tion of the alkaline-eliminant, less uric acid and more of the 
urea will be carried to the kidneys for excretion, thus limit- 
ing the work of elimination to the removal of the previously 
accumulated uratic excess. 

It will be seen that the final decrease in the urinary 
excretion of urates, observed after taking the alkaline-elim- 
inant a few days, may be attributed chiefly to two causes ; viz. : 
1 . The removal of all, or a part of the accumulated excess in 
the system. 2. The reduction in the amount of uric acid 
formed from day to day. This action is quite different from 
that of quinic acid. The latter, according to the claims of 
its German supporters (Weiss, Schlayer, and others), is 
said to decrease the excretion of urates by preventing the 
synthesis of uric acid from glycocoll and urea on reaching 
the kidneys. But the theory on which this supposed action 
is based has been shown to be unsound. No such synthesis 
occurs. Some experimenters (His, Foerster, Nicolaer, and 
others), have been unable to detect any variation in the 
excretion of urates after the ingestion of quinic acid; but, 
like tannic acid and other astringents found in the rind of 
certain fruits, skins of seeds, and bark of certain plants, it 
doubtless does produce such an effect, even in health — its 
action in that respect, probably, being much like that of the 
ordinary acid precipitant. 



276 URIC ACID AND ITS CONGENERS. 

The Objective Effect. — The objective effect ob- 
served from the use of the alkaline-eliminant is exactly the 
opposite of that from quinic acid. Concerning this latter 
agent, Ulrici has shown {Arch. f. experimen. Path. u. 
Pharm., XLVI, 321) that the ultimate effect is to actually 
increase above the normal the quantity of uric acid elimi- 
nated, after the withdrawal of the drug. He has demons- 
trated that the lessened excretion is only temporary; that 
the formation of uric acid in the system is in nowise af- 
fected; but that it becomes temporarily deposited in the 
tissues, or "locked up." 

In the opinion of many observers, such astringent 
principles, as the quinates, interfere with the absorption of 
food containing them; and the immediate decrease ob- 
served in the amount of uric acid eliminated in the twenty- 
four hours, means either a disturbance in the digestive 
tract, or a retention of the toxin in the body. The precipi- 
tant action of tannin on albuminous substances would seem 
to give some color to this assertion. 

"It is possible, moreover/' as one writer suggests, 
''that in introducing quinic acid, its equivalent alkaloid, or 
one of its salts, into the stomach, we are gratuitously 
furnishing the system an extra amount of purin material to 
be metabolized and eliminated at some future time, since it 
is known that the small amount of vegetable purins ingested 
as food is contained in the bark, rind, and peel. Like other 
vegetable alkaloids or extractives (e. g., as the xanthins and 
tannin of tea and coffee) quinic acid may tend to subalka- 
lize the blood and tissue juices and cause a precipitation of 
urates in the various connective tissues of the body, thus 
causing their disappearance temporarily from the urine, 
only to reappear in added amount when the normal blood 
reaction is restored. " 



THE ALKALINE-ELIMINANT. 277 

The fact will be readily appreciated that the objective 
effect of the alkaline-eliminant is just the reverse of all this. 
Instead of immediately lessening the amount of uric acid 
excreted in the urine, the effect during the first few days of 
its administration is to increase the elimination. Both 
bowels and kidneys are first " flushed out" in order to re- 
move the accumulated waste, soon after which a gradual 
reduction in the amount of urates excreted in the urine and 
feces will be observed. The stimulating effect on the meta- 
bolic function of the liver may be seen in the increased urea 
formation. In short, an agent is furnished which aids this 
much-abused organ in oxidizing the nitrogenous (purin) 
waste molecule into its normal end product. Furthermore, 
the alkalescence of the blood and tissue juices is increased 
instead of diminished, as may be seen from the lessened 
acidity of the urine — which may even become alkaline in 
reaction. An agent is thus given whose objective effect is 
to eliminate the existing "aetiological factor" from the sys- 
tem; not cause its retention. 

Two other important objective effects which should 
follow the use of the alkaline-eliminant, are (i) diuresis 
and (2) laxation. Victims of purin excess, in whatsoever 
stage, almost always suffer from the ill effects of retained 
sewage, both liquid and solid. The two channels of exit 
have become choked with cast-off material which cannot 
long be retained without causing toxaemic symptoms from 
the absorption of urinous (ammoniacal) exhalations and 
fecal sewer gas. While the choking up of the capillaries with 
uratic waste and colloid food detritus may be considered 
partially responsible for the inaction of kidneys and bowels, 
it should not be forgotten, that, at the same time, the chok- 
ing up of the two channels of exit react upon the capillaries 



278 URIC ACID AND ITS CONGENERS. 

themselves by interfering with the removal of their uratic 
obstruction, thus setting up a circulus vitiosus, which the 
true eliminant destroys by loosening up at both ends of 
the line. The need of such diuretic and laxative action is 
indicated by the concentrated, high-colored, odoriferous 
urine, and the still more concentrated malodorous material 
in the fecal reservoir, observed in the majority of cases of 
purin excess. 

By thus aiding the normal excretory functions of the 
organism, in the disordered condition which we have de- 
scribed elsewhere under the head of "hepatic-renal insuffi- 
ciency," any anti-uric-acid agent of the character under 
discussion becomes instrumental in removing the chief 
"predisposing aetiological factor" in cases of purin excess, 
which removal is essential to success in the treatment, 
especially in the last or "gouty" stage. 

Its Solvent Effects. — Notwithstanding the pro- 
nounced pessimistic views of the pure chemist, concerning 
the doubtful utility of introducing anything into the system 
with the object of increasing the alkalescence of the blood 
and its consequent greater solvency for the urates, we can- 
not blind ourselves to the well-established clinical fact, 
that, after the ingestion of the alkaline-eliminant, as well 
as many of the single alkaline salts (i. e., when taken in 
considerable dosage) as mentioned in the preceding 
chapter, strongly acid urine may be changed to a neutral, 
or even alkaline reaction. This means, if it means any- 
thing, that the blood brought to the kidneys, from which 
this urine is dialyzed, has suddenly become more alkaline 
than before. 

We know, too, that the urine of herbivorous animals 
is alkaline, and that their blood is consequently more 



THE ALKALINE-ELIMINANT. 279 

strongly alkaline in reaction to litmus than is the blood of 
carnivorous animals or of omnivorous man, with his acid 
urine. Again, we know that when the urates are not being 
excreted in normal amount in the urine during the twenty- 
four hours, the latter is overacid and that when an "ex- 
plosion "of urates occurs in a given case, the urine becomes 
temporarily more copious and less acid, or perhaps neutral. 

It is evident, therefore, that the reduction of urinary 
acidity is accompanied by a corresponding change in the 
degree of the reaction of the blood — i. e., it becomes more 
alkaline (there is less tendency toward acidulation). We 
cannot doubt that like other weak alkaline solutions whose 
alkalinity has been increased, such blood has also become 
a better solvent of the urates. At all events, clinical testi- 
mony supports this view, for the symptoms due to accu- 
mulation of urates at a given point speedily disappear, 
while the urine itself shows an increased excretion at the 
same time — just as an "explosion" of urates occurs as an 
attack is passing off. 

Still further, it has been repeatedly shown that even 
the crystalline biurates in the joints may be partially or 
wholly absorbed into the lymph and carried into the circu- 
lation, which has become a better diluent after administra- 
tion of the alkali. The same may be said concerning the 
solution of renal and cystitic concretions, in a urine made 
alkaline by the same means. 

Of course, the amorphous urates, which still remain 
in the blood in the capillaries in the form of a colloidal 
solution, are much more sensitive to this change in the 
blood's alkalescence and are removed more speedily and 
with less difficulty, as may be observed in the greater ease 
with which we afford relief to patients in the uricacidaemic 



280 URIC ACID AND ITS CONGENERS. 

stage. It is well known to chemists, that while the amor- 
phous and the crystalline forms of the acid urate have the 
same chemical composition, yet that the former have a far 
higher solubility. In fact when the amorphous urates are 
held in water or blood serum they form colloidal solutions 
which usually become supersaturated; and, under these 
circumstances, the crystalline form is readily precipitated 
out of solution. It has been demonstrated by Baumgarten 
that as soon as the amorphous form is washed free from 
impurities, further washing changes it to the crystalline 
form. This phenomenon has since been confirmed by the 
two eminent chemical authorities, TuniclifFe and Rosen- 
heim (Cf. Lancet, 1900, 1, 1708). 

Again, the solvent effects, or, rather, the oxidizing 
effects, of the alkaline-eliminant, is further observed in the 
increased cellular activity produced throughout the body. 
Owing to the raised alkalinity (or lessened acidity) of their 
environment, the individual tissue cells themselves possess 
greater enzymatic power. The hydrolytic enzymes or 
ferments secreted by the cells require a certain degree of 
alkalinity (or O H. ions) in their surroundings to become 
normally effective in metabolizing nitrogenous waste. 
The increased activity observed in this respect is partly 
due to the freer circulation through the capillaries, and 
partly to the greater solvency of the lymph and blood, both 
of which have become better diluents. Indirectly, there- 
fore, solvent effects are obtained by insuring a more com- 
plete cellular oxidation of purin waste, which being less 
colloidal, renders the blood less viscous and consequently 
a better solvent — at least, a better medium for conveying 
amorphous urates to the kidneys for final excretion. 

Methods of Administration. — Various methods 
of prescribing eliminants are in vogue. In the words of 



THE ALKALINE-ELIMINANT. 281 

von Noorden (Diseases of Metabolism: Saline Therapy, 
Part V, jS): "We know of a number of drugs, and we 
know of many measures, that are capable of increasing the 
uric acid of the urine for the time being, or of decreasing 
it. This means that by employing these remedies or 
measures we are able to 'wash out' the uric acid or cause 
its retention. We have every reason to include uric acid 
retention in the pathology of gout, and to welcome every 
measure that is capable of removing an excess of uric acid 
from the blood." 

Prof, von Noorden recommends saline mineral waters 
(as Homburg and Kissingen) for the above purpose. But, 
as stated by Prof. Jacobi and other eminent clinicians, the 
natural mineral waters have been found to be too poor in 
their alkaline ingredients to ever become very effective as 
uric acid eliminants. They are beneficial to a certain ex- 
tent, but enormous quantities must be ingested. The 
increased quantity of water excreted by this means serves 
a good purpose in some cases. As reported on a previous 
page, Jacobi recommends alkaline waters artificially pre- 
pared. 

In more recent years, the use of the simple alkaline 
salt, given singly, has been abandoned by the majority of 
practitioners, as being inferior to other methods. Even 
yet, however, a physician may have his favorite mode of 
combining two or more of the simple salts in order to ob- 
tain the effect of their conjoint chemical action, after ab- 
sorption. Prescriptions are sent to the local druggist, 
which call for the mechanical mixture of these salts, to be 
administered in powder form, or, perhaps, in some liquid 
combination. Pills and tablets containing the mechanical 
union of two or more simple salts, are also employed to 



282 URIC ACID AND ITS CONGENERS. 

some extent. It is a common practice, too, to better insure 
the absorption of these remedies by first cleaning out the 
intestinal tract with some cathartic agent. 

While these different methods have proven more or 
less satisfactory in a limited number of cases; nevertheless, 
owing to the crude union of the salts and their uncertain 
chemical action in the organism after absorption (when- 
ever such absorption really occurs), results, in many 
chronic cases of the rheumatic and gouty stages, have only 
been temporarily beneficial — recurrence of the attacks 
being very common. Evidently, in many instances, the 
improvement has been due to the establishment of a more 
active bodily metabolism, without succeeding in actually 
removing from the system the accumulated excess of 
urates. Therefore, as von Noorden truly says: "We 
have good reason to welcome every measure that is 
capable of removing an excess of uric acid from the blood.'' 



CHAPTER XXXII 



LITHIUM. 



Solvent Properties. — Of the various alkalies that 
may be employed in therapeutics to aid in the solution of 
uric acid and insure its elimination from the body by way 
of the urine, lithium, from the chemist's standpoint, 
should for various reasons be the most effective; and 
clinical experience has proven the correctness of this 
a priori reasoning. Even in average medicinal dosage 
and in the form of one of its simple alkaline salts (citrate, 
carbonate, benzoate, etc.), physicians have been enabled 
to neutralize the reaction of the urine without producing 
irritation of the stomach or the kidneys. 

Concerning the purely solvent properties of lithium, 
the following brief findings reported by professional 
chemists and pharmaceutical experts may prove some- 
what interesting; to wit: 

Gorsky (Centralblatt fur der med. Wissen, 28, 27) 
(1890) found increased uric acid excretion after LiC0 3 . 

PfeifFer (Verhandl. des 5/ Kongr. fur innere Medizin, 
444,) (1886), found after use of LiC0 3 , that less uric acid 
is given up to the uric acid filter (in the urine) than before 
the salt was administered. His finding has since been 
confirmed by Neumayer. From these results, both 
investigators have concluded that the dissolving power of 
the urine for uric acid is increased after ingestion of 
lithium. In other words, it has been shown that this 
alkali tends to prevent the deposition of uric acid calculi. 



284 URIC ACID AND ITS CONGENERS. 

W. His (Verhandl. des \%t Kongr. fur inner e Medizin, 
425,) (1900), found that the lithium salt shows an espe- 
cially great tendency to form neutralized solutions, in 
presence of the colloidal solution of amorphous urates. 

The fact is well known to chemists that lithium is by 
far the best solvent of uric acid in the test-tube. In short 
the dilithium urate (neutral urate of lithium), Li 2 (C 5 H 2 
N 4 3 ), is the most soluble of all urate salts. It is im- 
portant to note that when solutions of uric acid are to be 
utilized for injection into the body for experimental 
purposes, a solution of lithium urate is almost invariably 
employed. In his classical experiment for discovering 
the uric-acid-destroying power of the liver, Ascoli mixed 
blood with lithium urate and perfused it through the gland, 
finding that a considerable loss of uric acid occurred and 
that urea was correspondingly increased in amount. 

Prof. J. A. Patton, in considering the pharmacology 
of alkaline medication, classes the lithium salts among 
the so-called "indirect" alkalies. They are absorbed and 
oxidized in the blood and excreted as carbonates, diminish- 
ing the acidity of the urine and increasing the alkalinity 
of the blood. This increased alkalinity of the blood, 
he claims, promotes its oxidizing functions, as shown by 
the final decrease in the relative amount of the uric acid 
and an increase of urea eliminated in the urine. He has 
found that among these indirect alkalies, the lithium salts 
are much the best uric acid solvents. 

Combined with a Laxative. — Hutchinson (Jour. 
A. M. A., Dec. 3, 1904), voices the opinion of the majority 
of practitioners of America and Great Britain, when he 
says: "The 'old reliable' remedies in gout — in which 
great group the alkaline laxatives are most important — 



LITHIUM. 285 

have won their laurels, and enormously relieve the situation, 
by checking the acid processes of fermentation in the ali- 
mentary canal and sweeping the putrescent matters out of 
the system before they have time to give off their toxicant 
products to the blood. In short, almost every remedy" 
continues he, "which clinical experience has proved to be 
of value in gout and the gouty state will be found to prevent 
the fermentation or absorption of the intestinal toxins or 
to promote their elimination from the system" 

As previously stated in our chapter on /Etiological 
Therapy, that remedy will prove the most effective as an 
alkaline-eliminant in the treatment of purin excess which 
best succeeds in relieving the condition designated 
"hepatic-renal insufficiency," thereby removing the most 
important of the predisposing aetiological factors. Lithia, 
with or without some saline laxative, but preferably with 
it, as in thialion, has been found to be the most efficacious 
of the alkalies in removing this torpidity of bowels and 
kidneys, without resort to the drastic purgatives some- 
times used in such troubles. 

Sodio-Lithium. — Judging from personal experience 
and from the published reports of eminent clinicians at 
home and abroad, the so-called "laxative sodio-lithium 
salt" has been found to be more satisfactory for the 
purpose above referred to, than any of the simple lithium 
salts. This is a complex salt formed by the union of 
sulphuric and citric radicals (3 to 7) with sodium and 
lithium bases. 

In the preparation of this alkaline combination 
(thialion) it is said that the usual custom in manufacturing 
the simple alkaline salts is departed from. Instead of 
segregating the various products as they arise in the 



286 URIC ACID AND ITS CONGENERS. 

analytic process, the lithium base, in this instance, is left 
in chemical union with one of the residual products 
(sodium sulphate); thereby resulting in the production 
of a laxative salt, containing lithium and sodium, in which 
these two bases are in such relation that vital action is 
required to part them. Hence, in lieu of a mixture or 
mechanical combination of sodium and lithium salts, we 
have a new and complex combination in which the chemi- 
cal and therapeutic effects are necessarily sui generis. 

Its Chemical Action. — From the standpoint of the 
chemist it has been an interesting problem to account for 
the wide difference observed in the solvent and eliminative 
effects of this complex sodio-lithium salt, as compared 
with that following the use of any mixture or mechanical 
combination of the sodium and lithium salts, or with that 
of either salt when prescribed singly. Though only 
partially soluble in cold water, it is freely so in hot water, 
by which means it forms an artificial alkaline mineral 
water of unusual potency and solvent properties — thus 
coinciding with the views of Jacobi, as expressed in a 
previous chapter. Eminent clinical authorities agree that 
the solvent effects of this laxative salt are best obtained 
by administering it in hot aqueous solution in the pro- 
portion, approximately, of one to ninety (one heaped 
teaspoonful of the salt to a pint of water). 

After eight years of clinical demonstration, supple- 
mented by numerous laboratory tests, the generally 
accepted opinion concerning the chemical action (in the 
system) of this salt, as shown by the report of the chemist, 
is somewhat as follows: — Inasmuch as sodium sulphide is 
known to be discharged from the bowels, two or three 
hours after administration, it is evident that a portion of 



LITHIUM. 287 

the sodium must necessarily have been absorbed; which 
is supposed to have been made possible owing to the 
sulphuric radical of the salt uniting with both the sodium 
and lithium — i.e., so far as these bases are present in the 
proportion requisite for such purpose. That the absorp- 
tion probably occurs in this form is further indicated by 
the fact that the lithium, which is known to be eliminated 
chiefly by way of the kidneys, must also have entered the 
circulation; and such absorption would be much easier in 
the form of sodium-lithium sulphate than in the form of 
lithium citrate. (It should be explained here that chemists 
doubt if the sodium salt formed by the sulphuric acid is a 
neutral salt at the beginning; that probably an acid salt is 
the first member — not Na 2 S0 4 but HNaS0 4 — -in which case 
the sodium-lithium sulphate may readily be assumed, and 
in which form the lithium would be absorbed with com- 
parative ease.) From this, it is supposed that the citric 
radical then unites with the sodium ,to form sodium 
citrate, which is very readily absorbed. 

It will be seen from the foregoing description that 
eliminative action by way of the urine is two-fold; (i) 
lithium (a base) is free to unite with uric acid: (2) the 
citric radical, broken to carbonic acid, is free to unite with 
any base present in the blood (as waste product), and thus 
secure its elimination. These effects (produced in the way 
described) would seem to account for the observed clinical 
absence of any kidney irritation; though of course, such 
explanation is based chiefly on theoretical reasoning. 

While, as intimated elsewhere, the simple lithium 
salts, as ordinarily prescribed, do neutralize the urine to 
some extent and do increase temporarily the excretion of 
urates, nevertheless, the alkali is not absorbed in such 



288 URIC ACID AND ITS CONGENERS. 

form and in sufficient amount as to insure the removal 
of previously accumulated deposits in the joints and 
elsewhere, and, furthermore, does not promote the elim- 
ination of intestinal toxins from the system; but, in the 
laxative combination, as above described, not only is this 
latter desirable effect produced, but what is more import- 
ant still, the lithium is absorbed in toto. 



CHAPTER XXXIII. 



FINAL WORD. 



While it is admitted that there is yet no real consensus 
of opinion among scientists concerning the pathological 
importance of uric acid, and that the question of its metab- 
olism and clinical effects is still sub judice; nevertheless, 
it can no longer be doubted that the careful researches 
carried out in recent years point most unmistakably to 
the fact that it is one of the waste products of the human 
organism most frequently retained, and responsible for 
many of the common ills. 

Some writers do not freely accept this latter con- 
clusion, on the ground that autotoxaemia cannot properly 
be attributed to the action of a substance which is in itself 
non-toxic. This criticism, however, is made by the 
laboratory expert and not by the practicing physician. 
The latter knows from experience that any mechanical 
factor which interferes with the freedom of the capillary 
circulation, or which impinges as a foreign body upon the 
surrounding delicate tissues, even though it may be but a 
lump of innocuous jelly or crystal, will inevitably give rise 
to local and systemic disturbances, which, if not primarily 
toxaemic in character, are likely to become such by reason 
of the chemical and physical (pathological) changes 
induced. The septicemic condition caused by the 
presence of an innocuous foreign body in the vermiform 
appendix may be cited as an analogous case, — i.e., 
toxaemia due to a non-toxic factor. 



290 URIC ACID AND ITS CONGENERS. 

Some authors ridicule the idea of a "uric acid 
diathesis " It is true that the term has been used some- 
what loosely in medical literature, for the majority of 
physicians in employing this disease-name simply mean 
to infer that the patient is suffering from symptoms of 
uric acid retention and accumulation; that is, an acquired 
condition due to the fault of the individual, not a diathetic 
condition due to the fault of his construction, with which 
he was born and to which he has always been especially 
and peculiarly subject, — such as a strumous diathesis, 
for instance. 

Notwithstanding all this, it is by no means impossible 
that, in some instances, a uric acid diathesis may actu- 
ally exist. If, for one or more generations, the meta- 
bolic organs (especially the liver) have been persistently 
abused, by overeating, alcoholic excesses, sedentary life, 
etc., a weakened power to metabolize the purins into urea 
in the normal proportion (50 per cent.) may eventually 
result, and this weakness may become a family trait, 
transmitted from one generation to another. In short, 
the tendency to uric acid retention and accumulation may 
be handed down like any other physical, moral or intellec- 
tual tendency, — i.e., transmission of a metabolic weakness 
as well as a mental weakness. 

It is probable that no other subject :n physiology has 
received so great attention at the hands of scientific 
investigators in the last ten years, as has been devoted to 
the experimental study of uric acid metabolism. Several 
excellent original contributions have appeared in both the 
domestic and foreign medical journals, and not a few 
special treatises in the form of brief monographs. Some 
of these are invaluable to the student who wishes to gain a 



FINAL WORD. 291 

comprehensive knowledge of the subject. But the fact 
cannot be too strongly impressed upon the mind of the 
beginner, that it is a fault, or oversight, of many able 
modern writers to devote insufficient space to the con- 
sideration of one most important topic; viz: the destruc- 
tion of uric acid formed in the organism; i.e., its oxidation 
into urea (40 to 60 per cent.) before excretion. 

Owing to the above neglect, many conscientious 
physician-editors now entertain the idea (and so state in 
articles written for their journals) that it has been found 
that uric acid is not transformed in the body into urea. 
Knowing that the old theory (of uric acid being a half-way 
stage in the metabolism of albumin into urea) has been 
exploded, they are not aware that physiologists have 
demonstrated beyond cavil that uric acid is a half-way 
stage in the metabolism of nuclein or purins into urea. 
The fact is now well established that urea is the end pro- 
duct of nitrogenous catabolism, both albumin and purin. 

The significance of this knowledge to physicians 
becomes at once apparent when considering the subject 
of treatment. He should know that the liver is the organ 
chiefly responsible for the oxidation of uric acid into urea, 
and take such measures as are known to stimulate the 
performance of its enzymatic function. In other words, 
he should know that the employment of means to insure 
the oxidation or destruction of uric acid, is scarcely less 
important, from the therapeutic standpoint, than that 
which has to do with its elimination. 

The discoveries made by chemical experts, of the 
behavior of uric acid and its salts under various special 
conditions extra corpus, have led to a much more intelligent 
appreciation of the probable physiological and pathological 



292 URIC ACID AND ITS CONGENERS. 

purin changes which take place in the system. For exam- 
ple, it had been doubted by some physicians that uric acid 
could circulate in the colloid or amorphous form, since 
colloids were not supposed to dialyze. It has been 
shown, however, by the experimental investigations of 
His, Ord, Roberts, and others (Cf. Sir W. Roberts, 
Croonian Lectures, Lancet, 1892) that the amorphous 
form of the acid urate readily dialyzes, and that from such 
colloidal solutions (upon standing) the urates are grad- 
ually precipitated out in crystalline form. This precipita- 
tion is most likely to occur, or, rather, occurs most readily, 
when sodium salts are added to the solution. These 
chemical experiments point out the probability that uric 
acid circulates in the amorphous form and that colloid 
urates are dialyzed from the capillary blood into the lymph 
spaces or synovial sacs of the joints. As the fluids in these 
latter situations are oftentimes practically at rest, are rich 
in sodium salts and lack coloring pigment, the urates may 
readily become crystalline in these localities. 

Another chemical discovery of great practical signifi- 
cance, especially in pointing out the rationale of the 
alkaline treatment, is that reported by Croftan, who has 
studied the composition and mode of action of the liver 
ferment or "oxidase." He states that it consists of a 
nucleoproteid and albumose, each of which is dependent 
on the other; but the latter is the special agent in the 
oxidation process, — i.e., in transforming uric acid into 
urea. The albumose itself is held in solution by the pres- 
ence of certain salts. The nucleoproteid content simply 
acts as a carrier of oxygen, owing to its power of dissociat- 
ing H 2 2 — giving offO; and oxygen, of course, is essential 
to the enzymatic action of the albumose. He has found 



FINAL WORD. 293 

that while salts like the nitrates diminish this power of 
the nucleoproteids to liberate O, other compounds, such as 
the alkalies, greatly increase it. He suggests, and with 
much good reason, that the well known efficiency of the 
alkalies in the treatment of gouty affections may be 
connected with this action. 

Minkowski, in referring to the subject of treatment, 
says that the aims of therapeutics may be divided into 
three classes: — "i. Treating the primary defects in the 
metabolism. 2. Influencing especially the metabolism 
of the uric acid. 3. Treating the individual symptoms 
in different cases." {Die Gicht, p. 271). 

As to influencing the metabolism of uric acid, this 
eminent investigator believes that we should "endeavor 
to prevent the body from becoming highly charged with 
uric acid." To effect this desirable object he suggests the 
following four methods, viz: " (a) By decreasing the 
formation of uric acid; (b) by furthering the excretion; 
(c) by hastening the further oxidation; (d) by increasing 
the solubility of the uric acid in the blood and tissues." 

Von Noorden (Cf. Verhandl. des 14/ Kongr. fur 
inner e Med.) (1896) refers to the abnormal tendency, 
occurring in some cases, to form uric acid concretions. 
In considering the treatment, he says that we should 
"(1) give large quantities of water to increase the 
dissolving power of the urine for uric acid; (2) give such 
food as gives rise to little uric acid; (3) administer drugs 
which, after passing through the body, make the urine a 
better solvent for uric acid; keep out of the food, substances 
which, after passing through the body, make the urine a 
poor solvent for uric acid." 

In the "alkaline-eliminant" mode of treatment 
recommended in the preceding chapters of this work, it 



294 URIC ACID AND ITS CONGENERS. 

will be seen that the chief aims of therapeutics in gout, as 
above suggested in the words of Minkowski and von 
Noorden, have been kept constantly in view. The 
practical results obtained after several years' experience 
from the employment of this treatment by the author, 
urged him to investigate the subject more fully and 
determine, if possible, the modus operandi of the alkalies 
and discover whether they were used only empirically 
with merely accidental good effects, or if there was a 
scientific basis for such treatment which would prove its 
rationale. The reader is now left to judge for himself 
whether such a scientific foundation has been established. 

The richest single contribution in recent years to the 
subject of the aetiology of gout, or arthritis urica, is that of 
Prof. Lafayette B. Mendel, of Yale University, in an 
address delivered before the Harvey Society, at the New 
York Academy of Medicine (Cf. 'Journal American Med- 
ical Association, April 1906). By means of his laboratory 
experimentation, in conjunction with that of Prof. Chitten- 
den, it has been shown that after the ingestion of a purin 
meal (meat), a characteristic rise in the urinary excretion 
of uric acid in the healthy subject invariably occurs. The 
curve is especially well marked in those cases in which 
alcohol was ingested with the meal. 

In a gouty or rheumatic subject, however, it was 
observed that this postprandial curve was very much 
lessened; and, in some cases, did not appear at all. From 
these experiments, it has been demonstrated by Prof. 
Mendel, that the exogenous purins are excreted but poorly 
in cases of gout. The retention of uric acid is evidently a 
chief factor in the aetiology of this disorder. 

The various symptomatic ills, classed under the head 
of "purin excess/' have been considered here as one 



FINAL WORD. 295 

common disease-process, divided into three separate 
stages. While this is to some extent arbitrary, and is 
done for the greater convenience of the treatment of the 
subject and its better understanding; nevertheless, the 
clinical evidence is of a character that forces upon us the 
conviction that such a division is warranted, if not actually 
demanded, by the existing pathological conditions (both 
physical and chemical) as instigated by the processes of 
Nature herself. 

Again, uric acid has been considered in this work as 
an intermediate nitrogenous molecule, occurring seriatim 
during the physiological process of catabolizing or oxi- 
dizing the purins into urea — the true end molecule, which 
is much more easily dialyzed by the highly evolved epithe- 
lial cells of the human kidney. 

Lastly, it is intimated that in the general process of 
organic evolution, as the human organism becomes more 
thoroughly adapted to its internal and external environ- 
ment (the liver, especially, functionating to better effect as 
the individual learns how to treat it properly, and what 
quality and quantity of food substances to ingest), uric 
acid will eventually disappear as a waste product in the 
urine, except in cases of disease. According to the law 
of the "survival of the fittest," the more soluble and more 
highly oxidized nitrogenous end molecule, CH 4 N 2 0, 
will eventually be the only ureid excreted in health. 



BIBLIOGRAPHICAL AND GENERAL INDEX. 



A 

Acetic acid test for uric acid in 

urine, 140. 
Acid, absorbed into circulation from 
intestines, 89. 
behavior of pure uric acid, 27. 
dyspepsia in purin excess, 126. 
Adenase, a tissue ferment, 47, 64. 
.Adenin, a violent poison, 52, 53. 

changed into hypoxanthin and 

ammonia, 105. 
in walls of intestine, 46. 
Adenoids, due to uric acid reten- 
tion, 165. 
/Etiological Therapy, definition 
of, 245. 
summary of, 250. 
Albuminuria, in children, 163. 

in gout, 120. 
Albuminuric retinitis, 180. 
Alcohol, a cause of "next morning" 
headache, 97. 
effect of on liver, 82. 
inhibits action of uricolytic fer- 
ment, 97. 
its effect on kidneys in Bright's 

disease, 153, 154. 
its food value overbalanced by 

toxic effect, 83. 
lowers alkalescence of blood, 98. 
predisposing factor in gout, 120. 
Alkaline-eliminant, clinical purpose 
of, 274. 
consideration of, 274-282. 
laxative and diuretic effects 

of, 277, 278. 
methods of administration 

of, 280, 281. 
modus operandi of, 293, 294. 
objective effects of, 276, 277. 
stimulant action on liver, 277. 
solvent effects of, 278. 
Alkaline remedies, action of, 219. 
effects of, 264, 265. 

on genito-urinary concre- 
tions, 272. 
used as diuretics, 269. 
use of in purin excess, 270, 271, 
treatment in joint injuries, 190. 
Raynaud's disease, 204. 



Alkaline remedies, some spinal trou- 
bles, 199. 
of tooth disorders, 216. 
Alkalinity affected by absorption of 
acid intestinal juices, 82. 
of blood and tissue juices, 77. 
after absorption of urates, 91. 
reduced by exposure to 

cold, 81. 
reduced by muscular effort, 81. 
reduced by antipyretic 

drugs, 260. 
reaction, contradicted by 
Joulie, 267. 
of urine, due to fermentation in 
bladder, 133. 
when first voided, 133. 
Alkyl, a substitute radicle, 28. 
Allantoin, a di-ureid, 32. 

in cats and dogs, 53, 54. 
possible irritant of kidneys in 
Bright's disease, 153. 
Alloxan, a mono-ureid, 32. 
Alloxuric bases, their properties, 31. 

percentages in beers, 74. 
Alveolar abscess, causation of, 215. 
American Journal of Physiol- 
ogy, 45, 82. 
American Medical Association, its 

journal, 25, 284, 294. 
American Medicine, 93, 132, 197, 240. 
American Practitioner and 

News, 200. 
American Text-Book of the Diseases 
of Children, 162. 
of Operative Dentistry, 215. 
Amino, a substitute radicle, 28. 
Amino-oxypurin, chemical name for 

guanin, 29. 
Amino-purin, chemical name for 

adenin, 29. 
Amino-purins, disappearing from 

urine of man, 63. 
Ammonia, liberated during muscular 
strain, 105. 
during purin metabolism, 246. 
Amorphous urates, absorbability 
of, 258. 
dissolved in alkaline blood, 279, 
280. 



298 BIBLIOGRAPHICAL AND GENERAL INDEX. 



Amorphous urates, readily dialyze, 

292. 
Anaemia, symptoms of uricacidaemic 

stage in children, 160. 
Apoplexy, how occasionally caused, 

115. 

Approximate test for uric acid in 
urine, 140. 

Arch. f. experiment. Path. u. 
Pharm., 276. 

Archives of Pediatrics, 200. 

Aronsohn, accepts Garrod's teach- 
ings, 268. 

Arteriosclerosis, in gout, 120. 

Arthritis, disorders of, due to uric 
acid deposition, 219. 

Ascoli, discovered uric acid destroy- 
ing power of liver, 44. 
finds uric acid is oxidized in body 
into urea, 39. 

Asthma, a symptom of uric acid re- 
tention, 183, 184. 
bronchial, potassium iodide in, 

262, 263. 
in children, 163. 

precedes rheumatic attack in 
children, 109, 163. 

Astigmatism, relation of to uric acid 
retention, 182. 

Auto-intoxication, in relation to 
surgical procedures, 196. 

Autolysis, or auto-digestion of purins 
after animals' deaths, 49, 50. 

Autotoxaemia, due to a non-toxic 
factor, 289. 

B 

Backache, symptom of uric acid ex- 
cess, 197, 198. 

Baltimore, frequency of gout in, 120. 

Barbour, on growing pains of chil- 
dren, 200. 

Barley, a food now allowed in Japanese 
navy, 244. 

Bartels, his suboxidation theory, 15. 

Bate, on chronic Bright's disease, 149. 

Baumgarten, on amorphous 
urates, 280. 

Beebe, experiments with alcohol, 82. 

Beitrage zur Lehre vom Stoffwech- 
sel, 167. 

Bence-Jones, confirmed Garrod's 
findings, 16. 

Bergman, Prof. T. Olof., found uric 
acid in a cystitic calculus, 13. 

Beri-beri, dietetic treatment of, 243. 



Berliner K lini s c he Wo c hen- 

schri/t, 117. 
Beverages, tables of, showing 

amount of purin content, 74. 
Biliousness, symptoms of in purin 

excess, 138. 
Billings, Frank, on gout treat- 
ment, 266. 
Birds, serpents and fowls, uric acid 

metabolic end product of, 61. 
Bishop, his Diseases of Nose, Throat 

and Ear, 185. 
Bladder, irritability of neck of, 135. 
Blood, alkalescence of, 77, 

after taking the alkaline-elimi- 

nant, 279. 
reduced by antipyretics, 260. 
effect of alkalies on, 264, 265. 
its reaction, 267. 

its toxicity in normal preg- 
nancy, 171. 
pressure increased in menstru- 
ation, 168. 
why uric acid concretions do not 
form in, 115. 
Blues, fits of, their relation to uric 

acid retention, 98. 
Boston Medical and Surgical Jour- 
nal, 46. 
Bouchard, on resorption of toxins of 

body, 170, 171. 
Breton, Le, on orthopedic conditions, 

due to uric acid, 197. 
Brick-dust deposits in urine, 131. 
Bright's disease and eye affections, 
179, 180. 
causes and treatment of, 146-155. 
preceded by an auto-intoxication 
process, 129. 
British Lancet, on quadriurates, etc., 

28, 161, 280, 292. 
British Medical Journal, 168. 
Bronchitis, in children, 165. 
Bronson, on choroiditis, 181. 
Brooklyn Medical Journal, 160. 
Burian, R., demonstrates danger of 
lessened alkalinity of blood, 78. 
his feeding experiments, 37. 
his hypoxanthin-oxidase of mus- 
cles, 40. 
his theory of poverty of oxy- 
gen, 39. 
shows uric acid to be derived 
from muscle hypoxanthin, 66. 
shows uric acid to be derived from 
xanthin bases of meats, 19. 



BIBLIOGRAPHICAL AND GENERAL INDEX. 299 



C 

Caffein, its physiological effect, ioo. 
one-third of from coffee excreted 
as a purin body, 38. 
Calculi, in urine of infants and chil- 
dren, 162, 163. 
Campbell, his Auto-intoxication in 

Diseases of the Eye, 182. 
Capillary obstruction with colloid 

urates, 86. 
Carbohydrate elements in food of 

tropical regions, 227. 
Caries, of teeth, from systemic 

causes, 210. 
Cellular Toxins, by Vaughan, 150. 
Centbl. f. Bakt. u. Prasitkd., 78. 
Centralblatt fur die Medicin Wissen, 

271, 283. 
Charlotte Medical Journal, 196. 
Charcot, confirmed Garrod's find- 
ing, 16. 
Children, calculi in urine of, 162, 163, 
growing pains of, 199-201. 
purin excess in, 156-166. 
why more susceptible to uric- 
acidaemic stage, 159. 
Chinese, purin delicacies of the, 

227-229. 
Chittenden, Prof. R. H., accepts 
Garrod's teaching, 268. 
believes uric acid comes largely 

from muscle metabolism, 67. 
concerning intermediary purin 

metabolism, 46. 
his feeding experiments, 72. 
on subject of nutrition, 239, 240. 
on uric acid excretion in gout, 294. 
Chorea, of uric acid origin, 165. 

the urine in, 166. 
Choroiditis, due to uric acid excess, 

181. 
Oar, C, on action of alkalies, 271. 
Coffee, a cause of increased uric acid 

excretion, 72. 
Colchicum, objections to use of, 269. 
Collaemic disorders of uric acid 

origin, 219. 
Colloid urates, in uricacidaemic stage, 

87. 
Concretions, in toe joints, 115. 
Constipation, a causative factor in 
uric acid excess, 247, 248. 
due to retention of uric acid, III. 
sequela of purin excess, 122. 
Coryza, due to retention of uric acid, 
109. 



Coryza, may be rheumatic, 183. 
Croftan, Prof. A., experiments on 
guinea pigs, 119. 
on kidney troubles due to purins, 

151. 
on liver oxidase, its composition, 

292. 
shows lesions of renal cells, 69. 
shows uric acid changed to 
urea, 39. 
Croonian Lectures, by Sir William 

Roberts, 292. 
Cyclopaedia of Diseases of Children, 
by Keating, 157. 

D 

Dental conditions, in purin excess, 

207-215. 
Congress, Fourth International, 

209. 
Dental Cosmos, 210. 
Dentine, a poor thermal conductor, 208. 

how normally nourished, 211. 
Depression of spirits, preceding head- 
ache, 98. 
Diabetes, unfavorable for surgical 

operations, 194. 
Dialuric acid, a mono-ureid, 32. 
Die Gicht, 293. 
Diet and food, etc., 217. 

general rules for, 224. 
no-flesh, evils of a, 243, 244. 
Dietetics, for uricacidaemic patients, 

235, 236. 
general rules concerning, 234. 
Dilithium urate, solubility of, 284. 
Dimethyl xanthin, chemical name for 

theobromin, 29. 
Dimmock and Branson's test for uric 

acid, 142. 
Dioxypurin, chemical name for 

xanthin, 29. 
Diseases of Infancy and Childhood, 

by Holt, 157. 
of Metabolism, by von Noorden, 

281. 
Disorders of Digestion in Infancy 

and Childhood, by Fenwick 

and Lewis, 156. 
Di-ureids, contain four N. atoms to 

the molecule, 32. 
Dostal, on renal lesions from injec- 
tion of purin bodies, 69. 
Drummond, on aggravated uricacid- 

aemia in children, 161. 
Dyspepsia, of acid character, 126. 



300 BIBLIOGRAPHICAL AND GENERAL INDEX. 



Earp, Prof. Saml. E., on the murexid 

test, 139. 
Ebstein, concerning the tophi of 

gout, 118. 
Eclampsia, puerperal, how caused, 

174. 
Eczema, due to checked excretion of 

uric acid, 109. 
of children, 165. 
Ehrenfest, his theory of morning 

sickness in pregnancy, 172, 173. 
Elimination, essential before surgical 

operations, 193. 
English pediatricians, views of on 

rheumatism, 201. 
Environment, its relation to food 

requirements, 226. 
of American settlers, restricted, 

229. 
unlimited, of modern times, 229, 

230. 
Enzymes and ferments of tissues, 64. 
Erlenmeyer, his conical flask, 143. 
European clinics, statistics of, on 

eclampsia, 176. 
Evolution, explains why vena cava 

lacks valves, ill. 
theory of, 58. 
Exciting ^etiological factor of purin 

excess, 245. 
Excretory functions, aided by alka- 

line-eliminant, 278. 
Eye, disorders of, due to uric acid 

retention, 179-183. 



Fatigue, its setiological relationship 
to pain, 95. 

Feet, pains of, in rheumatic stage, 198. 

Fenwick, on uric acid infarcts of 
infants and children, 156. 

Ferments, intracellular, of the gen- 
eral tissues, 64 

Fischer, Emil, made purin syn- 
thetically, 28. 

Fcerster, concerning quinic acid, 275. 

Folin, his test for uric acid, 144. 

Food, a mixed regimen indicated, 
'230, 232. 
education, a system of required, 

233. 
for rheumatic stage, 237, 238. 
for uricacidaemic stage, 235, 236. 
in its relation to environment, 

226 228. 



Food purins, their ultimate fate in 

the body, 50. 
tables of, 73. 
Formative period, in gouty stage of 

purin excess, 90. 
Fourcroy, Comte de, found urea as 

decomposition product of uric 

acid, 13. 
Fowls, gout produced experimentally 

in, 117. 
Frerichs, on changes in alkalinity of 

synovial fluid, 92. 
showed uric acid to be trans- 
formed in body into urea, 14. 
Freudenthal, on coryza and asthma, 

183. 
Freudweiler, on tophi of gout, 118. 
Futcher, accepts Garrod's teachings 

on gout, 268. 
on frequency of gout in the 

United States, 120. 
on kidney insufficiency, due to 

uric acid excess, 127. 

G 
Galdi, finds uric acid excreted daily 

in feces of man, 45. 
Garrod, Sir Arthur, found uric acid 

in blood of gouty persons, 16, 

17. 
his thread test, 17. 
on uric acid excess and nephritis, 
127. 
Gangrene, resulting from capillary 

stasis, 195. 
Gaucher, injects xanthin, and hypo- 
xanthin, 119. 
shows lesions of renal cells from 
injection of purin bodies, 69. 
Genito-urinary concretions, how 
formed, 113. 
in concentrated urine, 114. 
influence of alkalies on, 272, 

273. 

German Archives of Clinical Medi- 
cine, Vol. I, 15. 

Glycocholic acid, in bile, 56. 

Glycocoll, 21, 33. 

Gcelet, Prof. Augustin PI., on abdom- 
inal operations, 196. 

Gcetze, maker of Hall's purinometer, 

145. 
Goiter, how sometimes caused, 169. 
in some spinal conditions, 198. 
Gorsky, on action of lithium, 283. 
Gout, characteristics of, 268. 



BIBLIOGRAPHICAL AND GENERAL INDEX. 301 



Gout, experiments in the production 
of, 117. 
excretion of uric acid in, 167. 
its frequency in United States, 

120. 
therapy of, 266-273. 
uric acid deposits in, 118. 
Gouty stage, dietetic treatment of, 
242, 243. 
formation of concretions in, 

factors favorable to, go, 92. 
manifestations of, 113. 
names of symptoms of, 256. 
of purin excess, 84-90. 
Gouty-pericementitis, 215. 
Greetzer, on uric acid infarcts of 
infants, 157. 
recommends water in infarcts of 
infants, 158. 
Graves' disease, how sometimes 

caused, 169. 
Growing pains, symptoms in rheu- 
matic stage, 199-201. 
Guanase, a ferment of tissues, 47, 64. 
Guanin, a direct irritant in intestines, 

52, 53- 
excreted in feces, 51. 
how changed to hypoxanthin and 

ammonia, 105. 
in walls of intestines, 46. 
Guano, as a fertilizer, 8. 

H 

Hahn and Nencki, show uric acid is 

changed to urea by the liver, 43, 
Haig, Alexander, believes uric acid 

circulates in solution with 

phosphates, 42. 
criticism of his works, 220. 
concerning Raynaud's disease, 

203. 
contradicts himself, 222. 
experiments with drugs, 225. 
his classification of uric acid 

disorders, 219. 
his mistake, 221, 222. 
his uric acid labors, 217-226. 
his uric acid theory, 218. 
his uric acid experiment, 25. 
on action of salicylates, 263. 
on drug action, 219. 
popularity of his works, 217. 
value of his work to clinicians, 

224. 
Haines-Bulkley Rule for estimating 

amount of solids in urine, 135. 



Hall, I. Walker, experiments con- 
cerning removal of purins 
from body, 50. 

experiments on rabbits, 151, 152. 

found one-half bound purins of 
flesh food excreted in 48 hrs. , 

51. 
his feeding experiments, 37, 72, 

his work on Purin Bodies in 

Food Stuffs, 53. 
invents the purinometer, 145. 
shows 40 to 60^ of uric acid to 

be changed into urea, in body, 

44- 
Hans, on uric acid retention in gouty 

people, 127. 
Hare, Prof. Hobart Amory, on uric 

acid excess in Bright's disease, 

155. 
Harley, his test for uric acid in 

urine, 142. 
Harvard Medical School, 243. 
Hawaii, purin delicacy of the natives 

of, 229. 
Hay-fever, due to checked excretion 

of uric acid, 109, 183-185. 
Headache, conservative of menstru- 
ation, 96. 
"next morning," after alcoholic 

debauch, 97. 
of uricacidcemic stage, how 

caused, 96. 
powders, their action in system, 

100. 
precedes uric acid explosion, 107. 
Heart failure, how occasionally 

caused, 115. 
Heat and acetic acid test for uric 

acid in urine, 140. 
Heintz, his test for uric acid in 

urine, 141. 
Hematuria, in children, 162. 
Hepatic insufficiency, a complication 
of gout, 125. 
torpor, its effect on uric acid 

excess, 137. 
renal insufficiency, a predispos- 
ing cause of purin excess, 247, 
248. 
Herter, C. A., on urine in chorea, 166. 
on urine in cyclic vomiting, 162. 
His, Jr., W., concerning quinic acid, 

275. 
his studies into physical chemis- 
try of uric acid,' 26. 



302 BIBLIOGRAPHICAL AND GENERAL INDEX. 



His, Jr., W., on action of lithium, 
" 284. 
thinks uric acid circulates in dif- 
ferent combination in gout, 
128. 
wonderful experiments of, 292. 
Holt, on urine of children in chorea, 
165, 166 
on urine of children in cyclic 

vomiting, 162. 
on urine of children in uricacid- 

aemia, 161. 
on urine of infants, 157. 
recommends water for uric acid 
infarcts, 158. 
Homburg, a natural alkaline water, 
recommended by von Noor- 
den, 281. 
Hopkins, his test for uric acid in 

urine, 144. 
Hoppe-Seyler's Zeitschrift fur phy- 

siol. Chemie, 40. 
Horbaczewski, obtained uric acid 
from spleen pulp, 18. 
showed that nuclein produced 
increased uric acid excretion 
in 2 hrs., 19. 
the first one to prepare uric acid 

synthetically, 21. 
thought uric acid was derived 
only from nuclein of leuco- 
cytes, 37. 
Hutchinson, on action of the alka- 
line laxatives, 284, 285. 
Hydantoin, a mono-ureid, 32. 
Hydro-carbon elements, in food, 226. 
Hydrochloric acid, used to acidulate 

urine, 141. 
Hydroxyl radicles. 26. 
Hydurilic acid, a di-ureid, 32. 
Hypoxanthin oxidase, cannot act 
efficiently without O, 41. 
formed from, muscles, 66. 
Hysteria, one of the neuroses, 102. 



Ibrahim, on uric acid injected sub- 

cutaneously, 40. 
Incidental ^etiological factors of purin 

excess, 249. 
Infarcts of uric acid in kidneys of 

fowls, 118. 
in kidneys of infants, 156. 
symptoms of, 157, 158. 
Inflammation, as a local symptom, 

253. 254. 



Inflammation, in treatment of, remove 
the cause, 257. 

Insomnia, cause of, 99. 

International Clinics, Vol. IV., 182. 

Internationa/ Medical Magazine, 192 . 

Intestinal lithiasis, 119. 

Intracellular ferments, of general 
tissues, 65. 

Ionic dissociation, in uric acid solu- 
tions, 26. 

Iritis, due to uric acid retention, 180. 

J 
Jacobi, Prof. A., on artificial alkaline 
waters, 265, 281, 286. 
on growing pains, 200. 
Japanese, food requirements of, 227, 
228. 
navy, food now adopted for, 243. 
Joints, injuries of and convalescence 
from, 188. 
treatment of, 190. 
Joulie, on neutral reaction of blood, 

267. 
Journal of Laryngology and Rhin- 

ology, Vol. III., 186. 
Journal of the American Medical 
Association, 25, 284, 294. 

K 

Keating, his Cyclopaedia of Diseases 

of Children, 157. 
on character of urine in infants 

and children, 163. 
on uric acid infarcts of infants 

and children, 157. 
Kidney, as a dialyzer or filter of 

urine, 79, 80, 147. 
cause of inflammation of in 

Bright's disease, 149. 
congestion of, 146. 
injured by salicylates, 266, 267. 
in true Bright's disease, 146, 147. 
in uricacidaemic and rheumatic 

stages, 154. 
its action stimulated before 

surgical operations, 193. 
its power of apparent selection, 

148. 
its power of excretion injured by 

purins, 150. 
no irritation of, from sodio- 

lithium, 287. 
of new-born infants, 156. 
osmosis of uric acid through epi- 
thelium of tubules, 148. 



BIBLIOGRAPHICAL AND GENERAL INDEX. 303 



Kidney, troubles of, in purin excess, 

127. 
work of as an excretory organ, 

127, 128. 
work of as an excretory organ 

to be favored in gouty stage, 

242. 
Kionka, H., his experiments upon 

fowls, 117. 
Kissingen, a natural alkaline water, 

recommended by von Noorden, 

281. 
Klemperer and Strauss, confirmed 

Garrod's findings, 16. 
Klemperer, Prof., on weak alkaline 

solutions of inorganic salts, 91. 
Kochmann, experiments on dogs 

with ox-flesh, 52, 53. 
Kolisch, on lesions of renal cells from 

injection of purin bodies, 69. 
on the injection of xanthin and 

hypoxanthin, 119. 
Kossel, obtained xanthin, hypoxan- 
thin, adenin and guanin from 

nuclein, 18. 
showed that meat increases uric 

acid excretion owing to its 

free xanthins, 19. 
Kowalewski, found uric acid in all 

nuclear tissues, 38. 
Kugelurate form of amorphous 

urates, 258. 

L 

Lancet (British), 28, 161, 280, 292. 

Lancet-Clinic, The, 149. 

Lautenbach, Prof. Louis J,, on 
astigmatism, 182, 183. 

Laxatives, effects of alkaline salts, 
272, 273. 
in lithaemic sore throat, 187. 

Le Breton, on orthopedic conditions, 
197-199. 

Leg-cramps, due to uric acid reten- 
tion, no. 

Lehmann, his Text-Book of Physio- 
logical Chemistry, 15. 

Levison, on action of salicylates, 263. 

Lewis, on uric acid infarcts of infants 
and children, 156. 

Lichty, considered uric acid w T as ex- 
creted as result of headache, 97. 

Lithemia, synonymous with uricacid- 
semia, 85. 

Lithemic gangrene, or Raynaud's 
disease, 204. 



Lithemic sore throat, Sir Morell Mc- 

Kenzie, 186. 
Lithiasis, in children, 162. 
Lithium, alkaline salt of, for uric 

acid infarcts, 159. 
combined with a laxative, 284,286. 
diurate, solubility of, 284. 
Haig's views concerning its 

action, 223. 
properties of, 283-285. 
salts of, in reducing acidosis, 

270, 271. 
urate of, injected intravenously 

into animals, 53. 
Liver, affected by toxic action of 

alcohol, 82. 
in uricacidsemic stage, 83. 
its relation to eclampsia, 175. 
oxidase of, 292. 
oxidizing function injured by 

sulphonal, 261. 
synthetic formation of uric acid 

in birds', 34. 
the human grate, 125, 126. 
the urea-forming organ, 137. 
torpid, to be stimulated, 275. 
Lorenze, E. J., reports case of uric 

acid infarcts in two infants, 

158, 159. 
Lowi, O., agrees with Hall, 44. 

believes nuclear uric acid derived 
chiefly from glandular organs, 

37- 

Ludwig-Salkowski test for uric acid 
in urine, 144. 

Luthje. on injurious action of salicy- 
lates, 266. 

Lymph, why favorable to uric acid 
concretions, 115. 

M 

Macalester, on uric acid retention in 

gout, 128. 
Macdonald, concerning leg-cramps, 

no. 
MacKenzie, Sir Morell, on lithemic 

sore throat, 186. 
Mackie, on adenoids, 165. 
Macleod, believes uric acid is derived 

chiefly from muscle metab- 
olism, 67. 
Manley, Prof. Thos., on joint 

injuries, 188. 
Mares, his feeding experiments. 37. 
Mathews, concerning constipation,. 

122. 



304 BIBLIOGRAPHICAL AND GENERAL INDEX. 



McCrudden, his book on "Uric 

Acid," 267, 270. 
McKinley, Pres., concerning the 

operation upon, 194. 
Meat, increases uric acid excretion, 

73- 
soups, solutions of xanthins, 241. 
tables of, showing purin con- 
tent, 73, 74. 
white vs. dark, 75. 
Medical Record, 170, 188. 
Mendel, Prof. Lafayette, accepts 
Garrod's teachings, 268. 
believes uric acid is derived 

largely from muscle, 67. 
his uricolytic ferment, 47. 
on the checked excretion of uric 
acid in gout, 294. 
Menopause, uric acid excess in, 177. 
Menstruation, experimental study of, 
167. 
retention of uric acid at begin- 
ning of flow, 97. 
Menu, for purin excess patients, 237. 
Metabolism, comparative, in animals, 

53- 
faulty, in uricacidcemic stage, 87. 
Methylxanthins, cause reflex irritabil- 
ity, 52. 
Microscopic examination, for uric acid 

in urine, 143. 
Miescher, on xanthin bases as decom- 
position products of uric acid, 
18. 
Migraine, followed by uric excretion 
in excess, 97. 
in children, 160, 161. 
in menstruation, 169. 
Miller, on tooth decay in rheumatism, 

210. 
Minkowski, gives adenin to dogs, 149. 
his feeding experiments with ade- 
nin and hypoxanthin, 38. 
on treatment of uric acid excess, 

293. 
shows pure albumin foods do not 

cause uric acid excess, 19. 
shows that, in gout, uric acid is 

in different combination, 128. 
supports Futcher's view, 127. 
Mono-oxypurin, chemical name for 

hypoxanthin, 29. 
Mono-ureids, two N. atoms to the 

molecule, 32. 
Montgomery, Prof., on surgical opera- 
tions, 192, 193. 



Morton, Sanford, on eye affections, 

180. 
Mucous membrane, a vicarious avenue 
for excretion of uric acid, 109. 
Murexid test for uric acid, 139. 
Muscle, defective nutrition of, 112. 
metabolism of uric acid, 40, 64, 

66. 
strain, and blood subalkalinity, 

104. 
when at work, increases hypoxan- 
thin, 40. 
Muscular energy minimized in the or- 
ganic evolutionary process, 60. 
stiffness, how caused. 

N 
Nencki, shows that uric acid is changed 

by liver to urea, 43. 
Nephrite epitheliale, a precursor of 

gout, 119. 
Neumayer, on action of lithium, 283. 
Neumeister, agrees with Hall, 44. 
Neuralgic twinges, in rheumatic stage, 

89. 
Neuroses, due to uric acid retention, 

102. 
Neurotic Disorders of Childhood, by 

Rachford, 150. 
New York Academy of Medicine, 239. 
New York and Philadelphia Medical 

Journal, 200. 
New York Lancet, 189. 
Nicolaer, concerning quinic acid, 275. 
Night terrors, of children, 161. 
Nitrogen, loses "explosive" action at 

moment of nuclein breakdown, 

67. 
retention and excretion in men- 
struation. 167, 170. 
Nitrogenous elements in food, 227. 
excreta, 7. 

food, excess of ingested, 239, 240. 
food elements, 227. 
waste, 55. 
Nomenclature, modern medical, 251. 
Northwestern Lancet, no. 
Nose, disorders of, due to uric acid 

retention, 183-186. 
Nosological basis of treatment, 251, 

252. 
Nuclease, a tissue ferment, 47, 64. 
Nuclein cleavage. 29. 

most of it absorbed from intes- 
tines direct into circulation, 
when fed to man, 51. 



BIBLIOGRAPHICAL AND GENERAL INDEX. 305 



Nucleo-proteids, 30. 
Nutrition, a study of, 239, 240. 

O 

Objective signs of purin excess, how 
caused, 246. 

Ocular inspection of urine, 131. 

phenomena, due to uric acid ex- 
cess, 179. 

Oliguria, favors formation of uric acid 
calculus, 114. 

Oliver, on high blood pressure in men- 
struation, 168. 

Omnipotent power, its impersonality, 
58. 

Operations, surgical, importance of 
elimination before, 193. 

Ophthalmic Review, 180. 

Opper, analysis of white and dark 
meats, 75. 

Ord, experimental investigations of, 
292. 

Osier, wards in Johns Hopkins Hos- 
pital, 120. 

Overeating, a causative factor of purin 
excess, 247. 

Oviparous animals, whose end prod- 
uct is uric acid, 8. 

Oxaluric acid, a mono-ureid, 32. 

Oxidase of liver, its character and 
function, 41, 292. 

Oxypurins, of meat, 49. 



Pain, howcausedinuricacidemicstage, 

95- 
in gout, a characteristic, 113, 115. 

Parabanic acid, a mono-ureid, 32. 

Parrot, on composition of uric acid 
infarcts, 156. 

Patton, Prof. J. A., on alkaline medi- 
cation, 284. 

Paul, on ionic dissociation, as applied 
to uric acid solutions, 26. 

Peirce, Prof. C. N., on pyorrhea areo- 
laris, 215. 

Peoria Medical Journal, 189. 

Pericarditis, often present in gout, 
120. 

Peridental membrane, an analogue of 
bone marrow, 207, 208. 

Pfeiffer, accepts Garrod's teachings, 
268, 269. 
on action of lithium, 283. 

Phelps, Prof. A. M., on joint injuries, 
189. 



Phosphates, Haig's views concerning, 
223. 

Piffard, on treatment of lithemic affec- 
tions of skin, 187. 

Pinard, on liver in eclampsia, 1 75. • 

Porter, Prof. W. H., on sprains and 
bruises, 188. 

Potassium iodide, in lessening viscos- 
ity of blood, 262, 263. 
salts, in lessening acidosis, 270, 
271. 

Practical Diagnosis, or the Use of 
Symptoms in the Diagnosis of 
Disease, by Hare, 155. 

Practical Medicine Series of Year 
Books (1905), Billings, 266,268. 
Pediatrics, by Grretzer, 157. 

Precipitant remedies, their action, 

274, 275- 
resembles quinic acid, 275. 
Precipitants, their action on urates, 
259, 260. 
therapeutic action, 219, 220. 
Predisposing factors of purin excess, 

247. 
Pregnancy, morning sickness of, 172. 

toxaemia, cause of, 171. 
Prevailing custom of treatment of 

purin excess, 258, 259. 
Proteid molecules, unstable, 67. 
Psoriasis, due to checked excretion of 

uric acid, 109. 
Puerperal eclampsia, how caused, 174. 

its treatment, 176. 
Purin delicacies, of modern times, 
231, 232. 
excess, an accumulation of uric 

acid and congeners, 84. 
feeding of American settlers, 230, 

231. 
foods, 72. 
tables of, showing contents of, 

73- 
free foods, from animal kingdom, 

241. 
free mixed diet, usually indicated, 

232. 
nucleus, 28. 
the three stages of "purin excess, " 

84. 
Purinometer, an instrument for de- 
tecting amount of purin bases, 

145. 
Purins and ureids, difficulty dialyzed 
by kidneys, 65. 
comparative metabolism of, 53. 



306 BIBLIOGRAPHICAL AND GENERAL INDEX. 



Purins and ureids, bound, exogenous, 

49- 
decimal decrease of, in urine, 62. 

free exogenous (excepting gua- 
nin). dissolved in intestinal 
juices, 50. 

pharmacological action of in body, 

5- 
unbound, exogenous, 48. 
unbound, exogenous, in feces, 45. 
unbound, exogenous, how re- 
moved by cooking properly, 
241. 
their removal from system, 63. 
their toxicity, 69. 
Purpurine, a pigment of urine, 21. 
Purpurate of ammonia, a di-ureid like 
uric acid, 32. 
in murexid test, 139. 
Purum uricum, 28. 

Pyorrhea Alveolaris, of constitutional 
origin, 215. 

Q 
Quinates, action of on the urates in 

the blood, 276. 
Quinic acid, its physiological effects, 

276, 276. 

R 

Rachford, his work on the Disorders 
of Childhood, 150. 

Ranke, confirmed Garrod's finding, 
and suggested that uric acid 
and hypoxanthin have a similar 
origin in body, 16. 

Raynaud, his Thesis, 203. 

Raynaud's disease, cause of, etc., 202- 
206. 

Reach, on uric acid retention in gouty 
subjects, 127. 

Reaction of blood, weakened, 79. 

Reference Handbook of the Medical 
Sciences, Vol. IV., 1S1. 

Remedies in common use, effect of, 
258-264. 
ill effects of, 260. 
temporary effects of, 259, 260. 

Renal inadequacy, 127. 

Retention cf solids in urine, 134. 

Revue de Therapeutique, 119. 

Rheumatic attack, from uric acid ex- 
plosion, 107, 108. 
joints, 188, 189. 
iritis, 180, 181. 
patients, proper food for, 237,238. 



Rheumatic stage, action of drugs used 
in, 262. 
growing pains a symptom of, 199- 

201. 
manifestation of, 104. 
names of symptoms in, 255. 
of Purin Excess, 84, 88. 
signs of, in children, 164. 
Roberts, Sir W., his quadriurate of 
soda, 28. 
investigations of, 292. 
Robinson, Prof. Byron, on uric acid 

calculus, 114, 132. 
Rockwood, E. W., shows endogenous 
excretion of uric acid differs 
or varies in different individu- 
als, 45. 
Romberg, on viscosity of the blood, 86. 
Rose, his ancient chemical treatise, 

222. 
Rosenfeld, on action of alkalies, 267. 
Rosenheim, expert opinion concerning 
quadriurates, 28. 
on amorphous urates, 280. 
Rosenquist, his analysis of white and 

dark meats, 75. 
Rosewater, on Raynaud's disease, 203, 

204. 
Ruhemann, invents the uricometer, 
144. 



Salicylates, action of (Salisbury) 266, 

267. 
effect of, on stomach and kidneys, 

263, 264. 
Saline therapy, von Noorden, 281. 
Salisbury, Prof. J. H., on action of 

salicylates, 266, 269. 
Salkowski, his theory that uric acid is 

derived from xanthin base, 17. 
with Ludwig, discovers test for 

uric acid, 144. 
Salomon, confirms Garrod's finding, 

16. 
Satterlee, on growing pains, 200. 
Scheele, Karl VVm., the discoverer of 

uric acid (1776), 13. 
Scherer, finds hypoxanthin in spleen 

of leukemic subjects. 17. 
Schiff, his test for uric acid in urine, 

142. 
Schittenhelm, finds uricolytic ferment 

in marrow of bones, 47. 
shows that normal feces contain 

purin bodies, 46. 



BIBLIOGRAPHICAL AND GENERAL INDEX. 307 



Schlayer, concerning quinicacid, 275. 

Schmiedeberg, on effects of purin de- 
rivatives, 150. 

Schmoll, E., believes uric acid circu- 
lates in combination with thy- 
minic acid, 41. 

Schrader, on nitrogen retention in 
menstruation, 167. 

Schreiber, on action of the salicylates, 
266. 

Schiir, feeding experiments of, 37. 
finds uric acid is derived from 
xanthin bases, 19. 

Sciatic nerves, tender points over, 198. 

Senator, casts doubt on Bartel's sub- 
oxidation theory, 19. 

Sheffield, translates Graetzer's book, 
from the German, 157. 

Silver nitrate test for uric acid, 142. 

Simon, Prof. Chas. E., believes all 

uric acid would be changed to 

urea, if all blood passed through 

the liver, 43. 

his Physiological Chemistry, 64. 

on blood reaction, 79. 

Siven, his feeding experiments with 
uric acid containing foods, 72, 

73- 

Skin, vicarious avenue of uric acid 
explosion, 108. 

Smith, L. B., a victim of joint injury, 
190. 

Smith, on urine in cyclic vomiting, 1 66. 

Sodio- lithium, its action, 285, 286. 

Sodium, salts of, in reducing acidosis, 
270, 271. 

Soetbeer, injects uric acid subcuta- 
neously, 40. 

Solvent effects of the alkaline elimi- 
nant, 278. 
properties of lithium, 283, 284. 

Special Creation theory, 57. 

Spencerian theory of evolution, 58. 

Spiegelberg, on uric acid infarctions of 
the new-born, 150. 

Spine and lower extremities, uric acid 
excess in, 197. 

Spitzer. found uric acid in all nuclear 
tissues, 38. 

Starr, Prof. Louis, on urine of chil- 
dren, 162. 

Stedman, on N. retention in men- 
struation, 170. 

St. Louis Courier of ALedicine, 173. 

St. Louis Medicaland Surgical Jour- 
nal, 190. 



St. Louis Medical Review, 243. 
Strauss, with Klemperer, confirmed 

Garrod's finding, 16. 
Sulfonal, effect on liver of mammals, 

54-. 
injurious action of, on liver, 261. 
relieves insomnia temporarily, 
101. 
Surgical procedures, how to prepare 

for, 192-194. 
Sweinitz de, Prof. G. E., on ocular 
symptoms in Bright's disease, 
180. 
Symptom therapy, 253, 254. 
Symptoms, localization of, in rheu- 
matic stage, 89. 
localization of, in uricacidaemic 

stage, 87. 
periodicity of, 102. 
Synovia, good locale for uric acid 

crystallization, 115. 
Syphilis, three stages of, similar to 
those of Purin Excess, 84, 85. 



Takaki, Baron, on foods of Japanese 

navy, 243. 
Talbot, Prof. Eugene, on constitu- 
tional causes of tooth decay, 209. 
Tandler, on injections of xanthin and 
hypoxanthin, 119. 
lesions of renal cells from injec- 
tion of purin bodies, 69. 
Tannin, precipitant action of, on al- 
buminous substances, 276. 
Taylor, feeding, experiments of, 72. 
Teeth, alkaline treatment of affections 
of, 216. 
anatomical divisions of, 207. 
decay of the dentine of, 209. 
disorders of, 207-215. 
gold filling, a good conductor, 

209. 
urate deposits in, 214. 
Temporary effects of antipyretic drugs, 

259- 
Theobald, on rheumatic iritis, 1S1. 
Therapie d. Gegemvart, 91. 
Therapeutic error, a source of, 252, 

253- 
methods of to-day, 251-258. 
Thialion, asan alkaline-eliminant,285. 
Throat, disorders of, due to uric acid 

retention, 186, 187. 
Thyroid gland, an organ of defense, 

169. 



308 BIBLIOGRAPHICAL AND GENERAL INDEX. 



Thyroid gland, enlarged during men- 
struation, 168. 

Tilney, W. T., a victim of joint injury, 
189. 

Tonsillitis, due to checked excretion 
of uric acid, 109. 
precedes rheumatic attack, 109. 

Toothache, symptom of uricacidsemic 
stage, 212, 213. 

Toxaemia, of pregnancy, 171. 

Transitional stage, in human evolu- 
tion, 59. 

Transition period, in rheumatic stage, 
88. 

Traumatisms, convalescence from, 
191. 

Treatment, of names of disease, 251- 
255. 

Trimethylxanthin, chemical name for 
caffein, 29. 
effect of on blood, 100, 101. 

Trioxypurin, chemical name for uric 
acid, 29. 

Tunicliffe, expert opinion on quadri- 
urate of soda, 28. 
expert opinion on amorphous 
urates, 280. 

Tyson, his Bright's Disease and Dia- 
betes, 180. 

U 

Ulcers, varicose, uric acid retention 

in, 192. 
Ulrici, concerning quinic acid, 276. 
Uratic deposits, 25, 80. 

absorbed, en masse, 82. 
after joint injuries, 191. 
cause of pain, 95. 
cause of tissue lesions, 119. 
from subalkaline blood, 81. 
in tissues of teeth, 214. 
localization of in gouty stage, 91. 
explosion in gout, 116. 
explosion, possible beginning of 

Bright's disease, 155. 
Urates, amorphous, absorbability of, 

258. 
amorphous or acid, 23. 
deposited in canaliculi of kidney, 

129. 
deposited in growing pains, 202. 
deposition of, causes muscular 

stiffness, 104. 
dilithium, most soluble of all 

urate salts, 27, 284. 
dinatrium, 27. 



Urates, explosion of, 98. 

explosion of, following migraine, 

97- 
held in solution in normal urine, 

43- 
heminatrium, 28. 
mononatrium, 27. 
of heavy metals, 124. 
of soda in intestinal walls, 123. 
precipitated in unusual localities, 

. II5 ' 
sites of, in rheumatic stage, 108. 

Urea, end product of albumin meta- 
bolism, 14. 

end product of all nitrogenous 
metabolism, 65, 295. 

its daily average excretion, 135. 

its daily average production, 130. 

retained in the organism, 129. 

retention of, in eclampsia, 176. 

retention of, prior to menstrual 
flow, 167. 
Ureids, nature of, 21, 32. 
Uricacidsemic manifestations, 95. 

patients, proper food for, 235, 236. 

signs, in diseases of infants and 
children, 159. 
.signs in pregnancy, 177. 

signs in Raynaud's disease, 205, 
206. 

stage and tooth decay, 211. 

stage of Purin Excess, 84, 85. 

stage, names of symptoms in, 255. 
Uric acid, An Epitome of the Subject, 
by Haig, 217. 

an intermediate product of purin 
metabolism, 54, 64, 295. 

a nitrogenous excrement, 7. 

a plant food, 8. 

As a Factor in the Causation of 
Disease, by Haig, 217. 

as a factor in choroiditis, 181. 

as an alkaloid of plants, 9. 

as a vestigial curiosity, 61. 

a simple test for, 145. 

attraction of its crystals, 25. 

causes first injury in Bright's dis- 
ease, 152, 153. 

causes symptoms of malaise, 52. 

concerning its synthetic forma- 
tion, 33. 

conditions usually unrecognized, 
197-206. 

crystallization in gouty stage, 92. 

crystals of, their color and shape, 
143. 



BIBLIOGRAPHICAL AND GENERAL INDEX. 309 



Uric acid, derivation from xanthin 
bases, 17. 

diathesis, how caused, 290. 

disease processes, due to its pres- 
ence in excess, 82. 

discoveries concerning, in later 
days, 291. 

dissolved, by alkaline eliminant, 
278, 279. 

early theory of origin of exploded, 
18. 

excess and food poisons, 218. 

excess, causes of, 71, 72. 

excess, three stages of, 84. 

excreted in excess as headache 
disappears, 97. 

excreted soon after ingestion as 
such, 50, 51. 

excretion, consideration of, 43. 

excretion, following lithium, 283. 

explosion, 107. 

formed faster than excreted, 150. 

free menu card, 237. 

how it circulates in the body, 41. 

in amorphous form, 280. 

in blood, increased in gout, 268. 

in colloid form, 56. 

increased by ingestion of alcohol 
with purin foods, 82. 

in human flesh food, 55. 

in its relation to astigmatism, 182. 

in its relation to growing pains, 
201. 

in its relation to hay-fever, 1.85. 

in its relation to jointinjuries,i88. 

in its relation to surgical opera- 
tions, 193-195. 

in its relation to the teeth, 2 10-2 16. 

in relation to varicose veins and 
ulcers, 192. 

infarcts in infants, 156. 

infarcts in infants, symptoms of, 

157. 
in feces, 45. 
injurious to cells of renal tubules, 

152. 
in Kugelurate form, 258. 
in meat (stake or bake) done rare, 

49- 

in urine, 21. 

its acid behavior, 27. 

its accumulation in the organism, 

68. 
its catabolism, 39. 
its chemical form in flesh food, 

55. 



Uric acid, its chemical properties, 27. 

its composition, 27. 

its crystallization and precipita- 
tion, 23. 

its crystallization in urine, 114. 

its cumulative action, 10. 

its decimal decrease in urine, 62. 

its decomposition in the organ- 
ism, 31. 

its discovery (1776) by Scheele, 13. 

its egestion vs. ingestion, 44. 

its elimination in pregnancy, 171. 

its endogenous origin, 37. 

its exogenous origin, 38. 

its experimental study, 290. 

its ionic dissociation, 26. 

its normal finding in the organ- 
ism, 68. 

its pathological importance, 289. 

its power for good or evil, 11. 

its purin structure, 28. 

its retention and excretion in 
menstruation, 167. 

its retention at the menopause, 
177. 

location of in flesh food, 10. 

location of in vegetable food, 9. 

metabolism and albumin meta- 
bolism, 19. 

McCrudden's treatise on, 267, 
270. 

of no use in the body, 68. 

of urine in children, 166. 

of urine in chorea, 165. 

of urine in cyclic vomiting, 162. 

oxidation of, into urea, 50, 291. 

physical appearance of, 21. 

produced from xanthins, 106. 

rational formula of, 29. 

recent findings concerning, 20. 

resorbed and eliminated, 125. 

retention and gangrene, 195. 

retention in constipation, 123. 

retention in muscular effort, 105. 

retention of in gout, 294. 

retention producing leg cramps, 
no. 

solubility of, 21. 

storms, preceded by depression of 
spirits, 98. 

Tables of, 73, 74. 

tests, Folin-Hopkins' method for 
expert laboratory work, 144. 

tests, general, 139-146. 

the early medical theory concern- 
ing, 14. 



310 BIBLIOGRAPHICAL AND GENERAL INDEX. 



Uric acid theory, of Raynaud's disease, 

203, 204. 
Uricolytic ferment, 47. 
Uricometer, instrument for testing for 

uric acid, 144. 
Urinalysis, general consideration of, 

I3I-I39. 

in cystitis, 133. 
in hepatic insufficiency, 138. 
preceding and following head- 
ache, 107. 
Urine, alkaline, due to volatile alkali, 

133. 

alkaline, of herbivorous animals, 
278, 279. 

alkaline, sign of cystitis, 133. 

cause of its acidity, 78. 

condition of, in uric acid explo- 
sions, 107. 

contains one part uric acid to 
1000, 114. " 

incontinence of, 136. 

in some spinal troubles, 198. 

its character in gout, 117. 

its ocular inspection, 131. 

its physical appearance during an 
attempted explosion, 131. 

its toxicity in pregnancy, 172. 

uric acid crystallization in, 114. 

V 
Varicose ulcers, retention of uric acid 

in, 192. 
Vaughan, his work on Cellular Toxins, 

150. 
Veal (bob-calves), contains greater 

percentage of purins, 75. 
Vegetables, Tables of, showing purin 

content of, 74. 
Vegetarianism, why unphysiological, 

228, 229. 
Vegetarian views of Haig, 224. 
Veit, his theory of immunization, 173. 
Verhandl. des Kongr. f. innere 

Medizin, 283, 293. 
Virchow, finds abnormal amount of 

uric acid in leukemia, 15. 
on clinical appearance of uric 

acid infarcts, 157. 
on composition or uric acid in- 
farcts, 156. 
Viscosity of the blood, 86. 



Visual irregularities, temporarily 
caused, 181. 

Vibert, on intestinal concretions, 119. 

Vogt, on uric acid retention in gouty 
subjects, 127. 

Vomiting, cyclic, of infants and chil- 
dren, 162. 

Von Fodor, demonstrates lessened 
alkalinity of blood, 78. 

Von Liebig, Baron Justus, investigates 
with Wohler, 14. 

Von Noorden accepts Garrod's teach- 
ings on gout, 268. 
blames alcohol for causing diffi- 
cult excretion of uric acid, 83. 
his Diseases of Metabolism, 281. 
on subject of treatment, 203. 

W 

Wakefield, on causation of gout in toe, 

93- 

Weidner, on action of salicylates, 263. 

Weiss, concerning quinic acid, 275. 

West, on composition of uric acid 
infarcts, 156. 

Wheeler, on asthma of children, 164. 
on rheumatism of children, 164, 

165. 
on uricacidsemia of children, 160, 
161. 

Wiener, believes in synthetic forma- 
tion of uric acid in body, 34. 

Wohler, Friedrich, on relation ©f uric 
acid to urea, allantoin, etc., 14, 

15. 
Wollaston, Wm. Hyde, found uric 
acid in gouty concretions, 13. 

X 

Xanthin bases, cause of pathological 
changes like ammonia, 70. 
early findings of, 17. 
effects of in body, 52. 
how changed to uric acid, 106. 
solutions of, as meat soups, 241. 
Xanthin oxidase of muscles, 47, 64. 
Xanthins, of tea and coffee, like 
quinic acid, 276. 



Zaudy, on action of the salicylates, 266. 
Zeitschrift fur physio I. Chemie, 40, 



OCT 24 190? 



